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Complex cell-state changes revealed by single cell RNA sequencing of 76,149 microglia throughout the mouse lifespan and in the injured brain
Open accessAbstract
Microglia, the resident immune cells of the brain, rapidly change states in response to their environment, but we lack molecular and functional signatures of different microglial populations. In this study, we analyzed the RNA expression patterns of more than 76,000 individual microglia during development, old age and after brain injury. Analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers. The greatest microglial heterogeneity was found at young ages; however, several states - including chemokine-enriched inflammatory microglia - persisted throughout the lifespan or increased in the aged brain. Multiple reactive microglial subtypes were also found following demyelinating injury in mice, at least one of which was also found in human MS lesions. These unique microglia signatures can be used to better understand microglia function and to identify and manipulate specific subpopulations in health and disease.
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TL;DR
Single-cell RNA sequencing of 76,149 mouse microglia across development, aging, and demyelinating injury identifies at least nine transcriptionally distinct microglial states, with the greatest diversity early in development and state shifts in aging and injury. The study defines state-specific markers, validates several populations by in situ hybridization, and finds a Ccl4+ microglial subset in mouse lesions and human multiple sclerosis lesions.
Key findings
- Across all ages and conditions, clustering revealed nine unique microglial states, with cluster sizes ranging from 0.2% to 24% of all microglia; canonical microglial genes were not uniformly expressed, as only C1qa, Fcrls, and Trem2 were expressed in all clusters.
- Microglial diversity was greatest at E14.5 and P5 and lower at P30 and P100; aging and injury redistributed states, including increases in Clusters 8 and 9. In aged P540 versus P100 mice, there were 2–4 times more microglia in aging-enriched Clusters OA2 and OA3, with OA2 expressing inflammatory genes such as Ccl4, Ccl3, and Il1b and OA3 expressing interferon-response genes including Ifitm3, Rtp4, and Oasl2.
- In LPC-induced demyelination at 7 days post-lesion, injury-responsive Cluster IR2 was almost entirely composed of lesion microglia and subclustered into IR2.1–2.4; IR2.2 upregulated Cxcl10, and IR2.2/IR2.3 upregulated Ccl4. IRM shared a 12-gene core signature with disease-associated microglia (DAM), including Spp1, Lpl, and Apoe, but also had unique interferon-response genes.
- Sex had almost no effect on microglial diversity or cluster proportions across E14.5, P4/P5, and P100; the only observed difference was female enrichment of the small Cluster Sx6 (~0.5% of microglia, observed only at P4/P5, enriched for Cd74, Ccl24, and Arg1). In human MS lesions, approximately 30% of microglia in the lesion were Ccl4+.
Methods
- Microglia were FACS-purified from C57BL/6J mice at E14.5, P4/P5, P30, P100, and P540, plus adult P100 mice after focal LPC-induced demyelination at 7 days post-lesion; at least three to four biological replicates per age were collected, totaling 76,149 sequenced microglia from 41 animals.
- Cells were processed with a droplet-based RNA-seq approach (10× Genomics Chromium), sequenced to ~40,000–60,000 reads/cell, and analyzed using an independent component analysis (ICA)-based clustering pipeline, including subclustering and canonical correlation analysis (CCA) for comparison with published DAM data.
- Findings were validated with single-molecule fluorescent in situ hybridization (smFISH), chromogenic in situ hybridization, and immunohistochemistry in mouse tissue, and with human MS tissue from the UK MS Tissue Bank; statistical analyses included ANOVA with Tukey’s post hoc tests, t-tests, and gene-marker thresholds of >1.5 fold change and P < 1E-4 with Benjamini–Hochberg correction.
Limitations
- Stated: further analysis is needed to establish whether the identified states are transient or represent terminal differentiation; lineage tracing is needed to determine the origin of Cluster 6 microglia and whether they give rise to mature microglia; manipulation of aged inflammatory microglia is needed to test whether they contribute to age-related brain inflammation; the small female-enriched Cluster Sx6 requires further validation; and whether other mouse lesion-enriched genes translate to human microglia needs confirmation.
- Evident: the main dataset is mouse-based, and the injury analysis focuses on a single model (LPC-induced demyelination) at one time point (7 days post-lesion); human MS validation was limited to five control/patient samples and centered on Ccl4/Tmem119 staining.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition to Ms4a7, Cluster 6 microglia also expressed increased transcripts of other Ms4a family members including Ms4a6c, Ms4a6b, Ms4a6d, Tmem176a, and Tmem176b (Fig 2a).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 6 microglia also upregulated chemokine (C-C motif) receptor 1 (Ccr1)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The top genes, including Fabp5, Mif, Ldha, and Tpi1, in Cluster 3 microglia were also upregulated in the Cluster 4 Spp1+ microglia found at P4/P5, albeit to a lower extent (Fig 4c, Fig S4b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At E14.5, approximately 1015% of all microglia belonged to Cluster 3 (Fig 4b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ms4a6c was also upregulated in microglia from the injured tissue (Fig 2c, Fig S4d)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and were localized in the brain using specific markers.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“at least one of which was also found in human multiple sclerosis lesions.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ms4a7+ microglia were most abundant at E14.5 (Fig 2e)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, pathway enrichment for M-phase, S-phase, and G-phase were represented to differing degrees in each subgroup (Fig S5a–c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which expressed unique sets of genes”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 3 microglia upregulate several other genes including macrophage migration inhibitory factor (Mif), lactate dehydrogenase A (Ldha), and triosephosphate isomerase 1 (Tpi1) (Fig 4a,c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Multiple reactive microglial subtypes were also found following demyelinating injury in mice”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we uncovered several large microglial subpopulations in the embryonic and early postnatal brain that expressed markers associated with metabolic activity, cell proliferation, cell growth, and cell motility”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we also identified genes strongly upregulated in, if not completely unique to, specific microglial states (Fig 1f, Table S1).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both aging and injury caused a redistribution of microglial states, including an increase in the percent of cells occupying Clusters 8 and 9, as compared to juveniles and adults (Fig 1d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“smFISH for Spp1 showed that these cells only resided in the subcortical axon tracts of the corpus callosum in the forebrain, as well as in distinct clusters in the axon tracts of the cerebellum (Fig 3d–f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metabolic pathways were also upregulated in both Clusters 3 and 4 (Fig S5d,e).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ms4a7 gene expression in microglia was most concentrated at E14.5 (Fig 2c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was striking diversity of expression on a cell-to-cell basis in these areas, with some microglia expressing high transcript levels of Spp1 adjacent to neighbors that had no detectable Spp1 expression (Fig 3f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“smFISH quantification confirmed the striking decrease in the number of Fabp5+Mif+ microglia between E14.5 and P30 (6% vs. <1% of all microglia) (Fig 4e,f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other upregulated transcripts in Cluster 3 microglia were associated with glycolysis”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other upregulated genes included insulin-like growth factor 1 (Igf1), glycoprotein (transmembrane) NMB (Gpnmb), and immunomodulators from the galectin family, galectin-1 (Lgals1) and galectin-3 (Lgals3).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Juvenile (P30) and adult (P100) microglia were largely assigned to three central clusters (Cluster 7a-c) that were not defined by any unique genes (Fig 1b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conversely, Cluster 3 microglia also expressed increased levels of the Cluster 4 markers Spp1, Gpnmb, and Igf1 (Fig 3c, Fig S4c)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that P2ry12, Cx3cr1, and Tmem119 (not shown) transcripts were expressed at much lower levels or not at all in certain clusters of microglia from the developing brain (Clusters 3,4).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 3 microglia were found almost exclusively at E14.5, although a small percentage were also present at P4/P5 (Fig 4b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The first subpopulation of microglia belong to Cluster 3 and uniquely express the gene Fabp5.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Non-microglial macrophages and monocytes uniquely expressed the genes coagulation factor XIII, A1 subunit (F13a1, macrophage), histocompatibility 2, class II antigen A, alpha (H2-Aa, macrophage), chemokine (C-C motif) receptor 2 (Ccr2, monocyte), lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1, macrophage), and macrophage galactose N-acetyl-galactosamine specific lectin 2 (Mgl2, macro”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster sizes ranged from 0.2% of all microglia to as many as 24% of all microglia.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These microglia expressed the gene secreted phosphoprotein 1 (Spp1), also known as osteopontin, at very high transcript levels (Fig 3c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our analysis uncovered at least nine transcriptionally distinct microglial states, which expressed unique sets of genes and were localized in the brain using specific markers.”
- Also stated in: another passage · plain
“Clustering analysis revealed nine unique microglial states across all ages and conditions, including injury (Fig 1b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: another passage · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The greatest microglial heterogeneity was found at young ages”
- Also stated in: another passage · plain
“We found the greatest microglial diversity at the youngest ages (E14.5 and P5) and considerably less diversity in juveniles (P30) and adults (P100) (Fig 1d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: another passage · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One subpopulation that was highly concentrated in aged mice was defined by the gene chemokine (C-C motif) ligand 4 (Ccl4, Cluster 8).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Injury Responsive Cluster 1 (IR1) was composed mainly of whole brain and saline-injected control microglia”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IRM uniquely upregulated interferon response genes including Ifi27l2a and Cxcl10.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that all three groups shared a common transcriptional signature of 12 core genes including Spp1, Lpl, and Apoe (Fig S7b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A comparison of saline-injected controls and LPC-injected animals showed a large increase in the number of Fcrls+ microglia throughout the demyelinated tissue”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that Cluster IR2-specific genes were variably upregulated among the microglia (Fig 6d)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found almost no difference in the clustering between the male and female samples (Fig S6b–d), as measured by the number of cells per sample in each cluster (Fig S6c) and the normalized number of cells occupying each cluster (Fig S6d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By age P30 and onward, only a few percent of cells fell into these proliferative clusters (Fig 4h)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we performed a second level of clustering analysis, called subclustering, on only Cluster IR2 cells (Fig 6e) and found several small subpopulations of IRM (Clusters IR2.1-2.4, Fig 6e).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and expressed high transcript levels of Spp1 (Fig S7h)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia from Cluster IR2.2 upregulated the interferon response gene Cxcl10 (Fig 6d,f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ccl4 staining was found in Tmem119+ cells”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two of the Injury Subclusters - IR2.2 and IR2.3 – specifically upregulated Ccl4 (Fig 6d,f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two microglia clusters were identified as being enriched in aging mice (Aging Clusters (OA) 2 and 3), along with one monocyte and macrophage cluster (Mono/Mac), which expressed the macrophage-specific markers F13a1 and Mgl2 (Fig 1f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster OA2 microglia also upregulated expression of the transcriptional regulator DNA binding protein inhibitor 2 (Id2) and transcription factor activating transcription factor 3 (ATF3) (Table S1)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Using this approach we found that DAM co-clustered with IRM in Microglia Comparison Cluster 2 (MC2) (Fig S7c,d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“subclustering of Cluster MC2 revealed that DAM largely fell into Clusters MC2.1, MC2.4, and MC2.5 (Fig S7e,f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They upregulated Lgals3, cystatin F (Cst7), chemokines Ccl4 and Ccl3, as well as the inflammatory cytokine interleukin 1 beta (Il1b) (Fig 5d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis of microglia from these three conditions produced two major clusters (Fig 6b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster MC2.2 upregulated genes include Cxcl10 and other interferon response genes”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we show in our dataset that microglia only express Arg1 in vivo in a very small subset of cells.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The only observed difference between the sexes was in Cluster Sx6, which was enriched in female samples.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Injury Subcluster 2.4 expressed cell proliferation markers, including Birc5”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster IR2 was almost entirely composed of microglia from LPC-injected demyelinated lesions (Fig 6c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster OA3 upregulated interferon-response genes including interferon induced transmembrane protein 3 (Ifitm3), receptor transporter protein 4 (Rtp4), and 2′-5′ oligoadenylate synthetase-like 2 (Oasl2) (Fig 5d,e).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which formed patches within the lesions, similarly to the smFISH analysis (Fig 7b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“each Injury Subcluster broadly upregulated Cluster IR2 genes, including Apoe (Fig 6f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also found an increase in the number of Ccl4+ cells (Fig 7d)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“smFISH showed that two of the selectively responsive genes – Ccl4 and Cxcl10 – were confined to small patches within the larger lesion (Fig 7b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Even with the shift, the number of microglia that occupy these states form only a small fraction of microglia”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and contained almost no DAM (Fig S7f,g).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IRM, however, were evenly distributed between all five subclusters (Fig S7f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“overall these results showed that microglial diversity was largely unaffected by sex during normal development.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, our data show that aging triggers a shift towards a more immunogenic profile including an increase in inflammatory microglia and interferon-responsive microglia.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ATM uniquely upregulated genes found in development, including Gpnmb and Fabp5.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, each group also expressed a number of unique genes.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in response to injury, some markers from both the proliferative clusters as well as the metabolically active cluster (Cluster 3) were slightly upregulated”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 2.4 was equally represented by IRM and DAM”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The OA2 microglia expressed a number of inflammatory signals which were not normally expressed by other populations of microglia in vivo (Fig 5d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we performed smFISH and chromogenic ISH for Ccl4 and Fcrls on P30 and P540 brain sections and found evidence of Fcrls+Ccl4+ cells throughout the adult and aged brain (Fig 5f,g).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Co-staining with human anti-Ccl4 antibody showed that Ccl4 was upregulated in the core of active lesions, compared to unaffected white matter in control patients (Fig 7f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 2-4 times more microglia in Clusters OA2 and OA3 from the P540 samples versus P100 controls (Fig 5b,c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both markers colocalized with Fcrls in many, but not all cases”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found a large increase in the number of Tmem119+ microglia in the core of the lesion, as compared to saline-injected controls (Fig 7d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Injury responsive microglia (IRM) in Cluster IR2 had downregulated expression of the canonical microglial markers P2ry12 and Cx3cr1”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017 source
- Not checked yetcites Salter and Stevens, 2017
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as well as a broad upregulation of Apoe in microglia (Fig 7a), which supports our sequencing data (Fig 6d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The same is true for the cell proliferation genes, which were upregulated to a smaller extent in the Cluster 3 Fabp5+Mif+ microglia (Fig 4c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They also uniquely upregulate interferon inducible protein 204 (Ifi204)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but our findings indicate that this profile is actually restricted to a small subset of microglia (Fig 5a,c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Very few Ccl4+Fcrls+ and Cxcl10+Fcrls+ cells were found in saline-injected controls compared to LPC-injected lesions”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which are also enriched in brain border macrophages.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both groups of cells upregulated similar genes including Apoe, Lpl, and Spp1.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“We found that microglial diversity is highest during early development, when microglia are still differentiating (Matcovitch-Natan et al., 2016).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Matcovitch-Natan et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ccl4+ cells were also found in blood vessels in control and MS samples (as seen at the bottom of the MS lesion image, Fig 7f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In total, approximately 30% of microglia in the lesion were Ccl4+ (Fig 7g).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The percentage of Ccl4+ cells away from the active lesions was comparable to that seen in control patient tissue”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Furthermore, these cells had a distinct metabolic signature.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“These signatures - cell cycle, phagocytosis, and surveillance - correspond with only three of the nine states presented here (Matcovitch-Natan et al., 2016).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Matcovitch-Natan et al., 2016 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The greatest similarity in cell state was found between P5 Cluster 6 microglia and microglia in the demyelinated lesion.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A major finding in our study was the identification of a subset of microglia that selectively express the chemokine Ccl4.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clusters 2 and 3 had considerable transcriptional overlap”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting an intermediate state (Fig 2g).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These unique gene expression patterns showed that each microglial state reflected a specific and definable transcriptional program, rather than a simple modulation of commonly expressed microglial genes.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“that could underlie the brain colonization process (Fig 4, Fig S5).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, this Spp1+ microglia population is highly concentrated specifically in the axon tracts of the pre-myelinated brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting an altered metabolic profile in these cells (Fig S5d)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“because it is likely that each of the proliferative clusters represent microglia at different stages of the cell cycle.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Their amoeboid morphology and their enrichment of genes associated with immune cell activation, lysosomal activity, and phagocytosis (Table S1, Fig S5e) suggest that ATM might engulf material in these regions.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“their restricted tempo-spatial appearance suggests that their activity is highly regulated.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the small percentage of Ms4a7+ cells at P30 likely represent perivascular macrophages.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that these pathways might become reactivated in pathology.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a transcription factor which could act as an upstream regulator of the IRM response to injury.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which could indicate that these cells flexibly enter and exit a proliferative state.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these two subpopulations of embryonic and early postnatal microglia likely play essential roles in controlling how microglia populate the brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“microglia play a dynamic role in physiological and injury-induced remyelination (Miron et al., 2013)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Miron et al., 2013 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“so it is plausible that Cluster OA3 microglia also play a role in contributing to the inflammatory tone of the aged brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
What the sources say
- Not checked yetcites Baruch et al., 2014 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the vast majority of microglia are unaltered or only slightly altered by aging”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Ccl4 is upregulated in the brains of Multiple Sclerosis (MS) patients (Szczucinski and Losy, 2007)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Szczucinski and Losy, 2007
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting the existence of subpopulations within the cluster”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We were able to recognize all of the same clusters that were identified in the larger analysis in Figure 1”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting possible reactivation of developmental pathways (Fig S3a,b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Therefore, the detection of localized populations of microglia expressing interferon-response genes may assist in identifying foci of neuronal injury or degeneration (Mathys et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
What the sources say
- Not checked yetcites Mathys et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“suggesting that microglia divide at an extremely low rate at older ages, an assertion supported by recent publications (Fuger et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
What the sources say
- Not checked yetcites Fuger et al., 2017 source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“LPC-induced demyelination is frequently used to study myelin repair and recapitulates many aspects of the demyelinated lesions found in patients with multiple sclerosis (MS) (Hammond et al., 2014).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Hammond et al., 2014 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“local cues like blood brain barrier compromise (Montagne et al., 2015) or microinfarcts (Smith et al., 2012) could drive state changes rather than a brain-wide shift.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these results suggest that activated microglia can respond in a diverse way to underlying pathological conditions.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we validated virtually all of the subpopulations using smFISH and antibody staining”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“our new cluster definitions highlight the greater degree of developmental complexity that were covered up by dominating signatures in bulk sequencing experiments.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Matcovitch-Natan et al., 2016 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The temporally and spatially restricted nature of these cells suggests extrinsic forces shape this state”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“These markers may comprise elements of a common activation pathway, since these genes are also upregulated in microglia that surround plaques in an Alzheimer’s disease model (Keren-Shaul et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Our cell clustering accurately represented the different microglial subpopulations in vivo.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“our detection of these cells in tissue using a different technique confirmed that the isolation of cells did not cause transcriptional artifacts.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies point to an important developmental role for these cells”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that microglia transition in and out of both states.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia are an especially attractive target for biomarker development and to monitor clinical progression because they can sensitively respond to changes in the brain that emerge before physical symptoms.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that specific subpopulations of microglia are similarly represented in mouse lesions and MS white matter lesions”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting this specific subset of microglia is only present in the lesion (Fig 7g).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, these results suggest that microglia ‘activation’ is a dynamic response involving transcriptionally and spatially distinct subpopulations.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and that they are the predominant source of Ccl4 in MS lesions.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 65
- Probably not a substantial claim. 31
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ms4a7+ microglia were sparsely distributed throughout the embryonic brain (Fig 2d,f), with a population of Ms4a7+ macrophages at the brain borders (not shown).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fabp5+Mif+ microglia were distributed throughout the E14.5 brain and often formed small clusters (Fig 4d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Markers for each of the proliferative populations were comparable in magnitude at E14.5 and P4/P5 and were highly specific to the proliferative clusters (Fig 4i, Fig S4a).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The top cluster markers for Cluster 2a were minichromosome maintenance complex component 6 (Mcm6), proliferating nuclear cell antigen (Pcna), and Rrm2. For Cluster 2b, they were Ube2c, baculoviral IAP repeat-containing 5 (Birc5), and H2A histone family, member X (H2afx), and for Cluster 2c they were histone cluster 1, H2bc (Hist1h2bc), cyclin B2 (Ccnb2), and Cenpa.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 9 was composed predominantly of microglia from the focal white matter injury and had increased expression of the gene interferon, alpha-inducible protein 27 like protein 2A (Ifi27l2a).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At P4/P5, we found one major microglial state (Cluster 4) that was barely found at any other time point (Fig 3a,b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The axon tracts where ATM were concentrated will eventually become heavily myelinated, but ATM are largely gone before myelination occurs.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At E14.5, the most populous microglial states were proliferative (Clusters 2a,2b,2c) and comprised a total of approximately 40% of all E14.5 microglia and 35% of P5 microglia (Fig 4g,h).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“several states – including chemokine-enriched inflammatory microglia – persisted throughout the lifespan or increased in the aged brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 6 microglia were predominantly from E14.5 versus any other age or condition analyzed, as approximately 10% of all E14.5 microglia (but no more than 3% of microglia at any other age) fall into Cluster 6 (Fig 2b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Gene expression analysis showed that the canonical microglial genes (Fcrls, P2ry12, Cx3cr1, Trem2, and C1qa) were highly expressed by most of the analyzed cells, but only three (C1qa, Fcrls, Trem2) were uniformly expressed in all clusters (Fig 1e)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Some clusters were dominated by microglia from specific ages, whereas others contained microglia from several ages”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A small percentage (0-3%) of non-microglial monocytes and macrophage populations were also found (Cd45high cells) but were left in the clustering analysis to provide a point of reference for comparison with the various microglial states (Fig 1b,g, Mono/Mac cluster).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Isolation of microglia to minimize ex vivo activation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These cells, which assume an amoeboid morphology (data not shown), also upregulate the lysosomal markers lysosomal-associated membrane protein 1 (Lamp1) and Cd68 (Table S1, Fig S5e)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Specialized axon tract–associated microglia (ATM) appear during a restricted developmental window
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At E14.5, we identified a distinct subpopulation of microglia that uniquely express Ms4a7 and share a similar transcriptional profile with brain border macrophages (Fig 2, Cluster 6).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data show that this unique population of Fabp5+Mif+ microglia was found almost exclusively in the embryonic brain and were not restricted to a particular brain region.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 8 cells were found at most ages, albeit in smaller numbers, with a developmental peak at P5.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Aging did not lead to the appearance or disappearance of any clusters, but rather caused a progressive expansion of clusters that typically have few very cells in adolescent and adult samples (P30 and P100, Fig 1d) (Fig 5a–c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster Sx6 is the smallest identified microglial cluster (~0.5% of microglia), was observed only at P4/P5 (Fig S6c–d, Fig 1d), and was enriched for the genes Cd74, chemokine (C-C motif) ligand 24 (Ccl24), and Arg1 (Fig S6e).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These clusters represented P2ry12high (MC2.1, data not shown), Spp1high (MC2.4, Fig S7h), and Ccl4high (MC2.5, data not shown) microglia.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we used chromogenic ISH and found a significant upregulation of doublepositive cells in P540 brains (Fig 5h), however no significant differences in regional distribution were found.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ccl4+Fcrls+ microglia were distributed amongst the other microglia but were otherwise indistinguishable (Fig 5f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“microglia from males uniquely expressed the Y chromosome gene Eif2s3y and microglia from females expressed the X inactivation gene Xist (Fig S6f).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were very few Ccl4+ microglia in the healthy developing brain, with a small developmental peak at P5 but a large increase in the percentage of these cells was found in the P540 brain (Fig 1d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a portion of the Cluster 3 microglia physically cluster with the proliferative microglia (Fig 1b) and were also enriched for degradation pathways for mediators of proliferation (Fig S5d)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a gene also expressed by proliferative microglia during early brain development (Fig 4g)”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The top cluster markers in Clusters 2 and 3 also shared some transcriptional overlap. For example, Mif, Ldha, and Tpi1 were also expressed by proliferative microglia but to a lesser degree (Fig 4c,i).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We defined at least 9 subpopulations of microglia and provide unique transcriptional and spatial signatures that give us hints about their possible functions.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These microglia are present in small numbers during development and expand in two different contexts: aging and injury.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we identified a unique microglial state (Cluster 6) that was enriched at E14.5 and defined by the genes Ms4a7, Ccr1, and Mrc1”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
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In the paper
“we also found that injury-responsive microglia upregulated other pathways found in developmental subpopulations including markers of proliferation (Birc5), metabolic activity (Cluster 3 microglia [Mif]), and those belonging to the Ms4a family (Ms4a6c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that microglia responding to injury do re-express developmental markers, but their transcriptional states do not completely overlap.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other key microglial states in early development were enriched for pathways associated with cell metabolism, growth, motility (Cluster 3) and proliferation (Clusters 2a-c) and were scattered throughout the brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found that the only microglia enriched for inflammatory signals are in Cluster 8/Cluster OA2/Cluster IR2.2, IR2.3 and express Ccl3, Ccl2, Ccl7, Ccl9, Ccl12, Il1b and Tnf.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ccl4 staining was found predominantly in Tmem119+ microglia, although a small percentage of Ccl4+/Iba1+ amoeboid immune cells were also observed (data not shown).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The other microglial subpopulation in the developing brain, Cluster 4, was restricted to unmyelinated axon tracts at P4/P5 and assumed a highly activated profile”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting an overlapping transcriptional signature and possible relationship between the two states.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“For both rounds of analysis, independent components that captured batch or replicate effects were removed before clustering analysis (Fig S2d), as previously described (Saunders et al., 2018).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Isolation of microglia to minimize ex vivo activation
What the sources say
- Not checked yetcites Saunders et al., 2018 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these data demonstrate that microglia exist in multiple definable states that change over the course of development, aging, and injury.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, these results identify Cluster 6 microglia as a subpopulation that reside in the embryonic brain parenchyma and bears considerable transcriptional overlap with brain border macrophages.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that some microglial states are present across development while others are more transitional (Fig 1c,d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that existing tools and marker definitions may need to be updated.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To ensure this step did not affect our recovery of microglial subpopulations, we Percoll purified microglia at P5, when we see considerable microglial diversity, and compared these microglia to those isolated without Percoll – finding no change in the subpopulations present and only a slight shift in the relative percentages of microglia in one of the nine clusters (Fig S1).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Isolation of microglia to minimize ex vivo activation
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these data provide a comprehensive map of these changes and identify genes that define several of these specific microglial states.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Distinct microglia subpopulations with unique transcriptional signatures peak in number during early development
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“at least three to four biological replicates per age were collected for a total of 76,149 sequenced microglia from 41 total animals (Fig 1b).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Isolation of microglia to minimize ex vivo activation
Strength:plain· not yet calibratedn = 41Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cells were sequenced to comparable sequencing depths (~40,000–60,000 reads/cell), and had a similar median unique molecular identifier (UMI) count and median gene number in all ages and conditions (Fig S2a).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Isolation of microglia to minimize ex vivo activation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“These differences found by smFISH closely mimic the percentages of Ms4a7+ microglia found in our sequencing data and confirm that these cells are present in the developing brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia were marked by Fcrls, which was uniformly expressed by all microglia in every cluster (Fig 2d).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > A population of embryonic Ms4a-expressing microglia share a similar transcriptional profile with brain border macrophages
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The widespread distribution of both proliferative and metabolically active microglia suggests that both cell subtypes give rise to mature microglia in the adult brain, but lineage tracing studies will be needed to track their progression.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Microglia expansion and distribution fueled by metabolically active and proliferative microglia in early development
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that microglial activation is a tailored response in which microglia activate both generalized and selective transcriptional programs.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“suggests that this small subpopulation of microglia contributes to age-related brain inflammation; however manipulation of these microglia will be essential for testing this hypothesis.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
What the sources say
- Not checked yetcites Franceschi et al., 2007 source
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true.
In the paper
“since its expression is maintained by resident human microglia in MS lesions and is not expressed by infiltrating immune cells (Zrzavy et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Zrzavy et al., 2017 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This quantification supports our sequencing data and shows an increase in the number of Cluster OA2 microglia with aging.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Small populations of inflammatory and interferon-responsive microglia emerge in the aged brain
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that these effects were in response to demyelination and were not a consequence of the injection (Fig 7c).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and was perinuclear, most likely in the Golgi, where cytokines are often packaged into vesicles for release.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Another major class of activated microglia called Disease Associated Microglia (DAM) were recently identified in a mouse model of Alzheimer’s disease (5xFAD) (Keren-Shaul et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 49,445 cells were clustered together across all the ages and sexes.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Sex has no impact on microglial diversity or the number of cells in each subpopulation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting other cells might also upregulate these pathways.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The images were coded to obscure the identity of each sample as well as the probes used. A blinded researcher used the manual counting feature in ImageJ to count cells labeled with green substrate (Ccl4+) or co-labeled with green and red substrate (Ccl4+Fcrls+).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results suggest that microglia assume many distinctive states that change over time”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Re-expression of these markers could be an integral part of the activation process and might be necessary to stimulate a quick response to pathology.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“blocking TGF-beta signaling (which helps to confer microglia identity, (Butovsky et al., 2014)) has no major effect on microglia cell number, but causes a drastic shift in their gene expression including widespread upregulation of (or failure to downregulate) genes found in Cluster 6 microglia and in brain border macrophages, including Mrc1 (Wong et al., 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“microglia become activated and aberrantly remove synapses in the early stages of pathology in mouse models of Alzheimer’s disease, well before cognitive decline and plaque formation (Hong et al., 2016).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Hong et al., 2016 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“identification of robust markers for different microglia states in disease will allow for the development of tools to more specifically track and visualize microglial activation, inflammation, and disease progression.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which could mean that markers of these unique – and potentially pathogenic – microglia could be used as biomarkers or therapeutic targets.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Results: > Diverse microglial activation responses are triggered in demyelinated mouse lesions and human MS tissue
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
In the paper
“evidence of aberrant microglia activation has been found in many forms of neurodevelopmental and neurodegenerative disease, but the diversity of these responses and specificity of the microglia response to each disease needs further exploration (Salter and Stevens, 2017).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Salter and Stevens, 2017
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Pathway analysis was performed using Hypergeometric testing and a Benjamini Hochberg correction for multiple testing.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“ICs corresponding to batch or replicate effects were removed from analysis, and the cells were then clustered based on their values for the remaining ICs.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Brain tissue was obtained through a UK prospective donor scheme with full ethical approval from the UK Multiple Sclerosis (MS) Tissue Bank (MREC/02/2/39).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Current PET imaging ligands, including TSPO, are not selective for microglia and are better markers of neuroinflammation (Politis et al., 2012).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Politis et al., 2012 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, the ACD 3-plex negative control probe was used on one section per slide to confirm signal specificity.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > METHOD DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed spectral gating on the LSM 710 microscope to narrow the collected emission spectra for the Alexa 488 and Atto 550 dyes and to minimize the autofluorescence.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > METHOD DETAILS
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These microglia could also arise from ontologically distinct progenitors”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“recent transplantation experiments suggest that Ms4a7 and other markers in Cluster 6 are specific to hematopoietic derived cells versus those derived from yolk-sac progenitors (Bennett et al., 2018).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Bennett et al., 2018 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Ccl4 antibody specificity was tested using secondary antibody only controls as well as with antibody preadsorption using recombinant Ccl4 protein, as previously described (Sekar et al., 2016).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > METHOD DETAILS
What the sources say
- Not checked yetcites Sekar et al., 2016 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All experiments were reviewed and overseen by the institutional animal use and care committee at Boston Children’s Hospital in accordance with all NIH guidelines for the humane treatment of animals.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“states that can be defined by unique markers and localized within the brain.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Another group showed that these microglia were the predominant source of Igf1 in the early postnatal brain, and Igf1 conditional knockout in microglia affected the health of developing cortical neurons at the same age (Ueno et al., 2013).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Ueno et al., 2013 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Metabolic state is directly manipulated by cytokine and pattern-recognition receptors, and elevated glycolytic activity has been tied to immune cell activation (Everts et al., 2014; O’Neill and Pearce, 2016).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
- Not checked yetcites Everts et al., 2014 source
- Not checked yetcites O’Neill and Pearce, 2016
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The RNAscope® 2.5 HD Duplex Detection Kit (Chromogenic) was used in experiments involving 18 month-old mice to avoid autofluorescence from lipofuscin accumulation in the aged brain (Xu et al., 2008).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
What the sources say
- Not checked yetcites Xu et al., 2008
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Many of the signals expressed in this subpopulation can be highly damaging to the brain. For example, Il1b and Tnf can both cause neurotoxicity (Takeuchi et al., 2006; Ye et al., 2013), and infiltrating immune cells attracted by the chemokines expressed in the Ccl4+ subpopulation can exacerbate pathology (Gadani et al., 2015).”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The ACD 2-plex negative control probe was used on one section per slide for control purposes.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Genes that define each cluster of microglia exceed a minimum threshold of 1.5 fold change and a P-value less than 1E-4 and were adjusted using Benjamini–Hochberg false discovery rate (FDR) correction.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > STAR Methods > QUANTIFICATION AND STATISTICAL ANALYSIS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is possible that they are a specialized group uniquely primed to produce an inflammatory response.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These microglia, which were present in the brain parenchyma, could be microglia that have yet to fully differentiate.”
§ Single cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes > Discussion
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Microglia rapidly change states in response to their environment.
“Microglia, the resident immune cells of the brain, rapidly change states in response to their environment”
The paper relies on this without support.
There is a lack of molecular and functional signatures of different microglial populations.
“but we lack molecular and functional signatures of different microglial populations”
The paper relies on this without support.
Microglia have historically been characterized as resting, M1, or M2 based on simple in vitro stimulation methods.
“microglia have historically been characterized as ‘resting’, ‘M1’ (proinflammatory), or ‘M2’ (anti-inflammatory) - based on simple in vitro stimulation methods.”
The paper relies on this without support.
It is still unclear when microglia diverge from brain border neighbors and how quickly they differentiate.
“However, it is still unclear when microglia diverge from their brain border neighbors and how quickly they differentiate.”
The paper relies on this without support.
It is not until microglia infiltrate the brain parenchyma and are exposed to brain-derived signals that they achieve their unique identity.
“It is not until microglia infiltrate the brain parenchyma and are exposed to brain-derived signals that they achieve their unique identity.”
The paper relies on this without support.
The extent of the microglial response to aging has not been comprehensively studied, and it remains unclear how, where, and to what extent microglia change with normal aging.
“However, the extent of the microglial response to aging has not been comprehensively studied, and it remains unclear how, where (in the brain), and to what extent microglia change with normal aging.”
The paper relies on this without support.
It is unclear whether microglia tailor their responses to specific injury types or whether distinct microglial populations exist in pathological tissue.
“However, it is still unclear whether or how microglia tailor their response to specific injury types or whether distinct populations of microglia exist in pathological tissue, as we lack both the markers and tools to identify and characterize different activation states, should they exist.”
The paper relies on this without support.
Microglia respond robustly and rapidly to demyelination in the LPC model.
“third, microglia respond robustly and rapidly to demyelination in this model”
The paper relies on this without support.
Microglial activation is largely confined to the lesion where demyelination occurred.
“microglial activation is largely confined to the lesion where the demyelination has occurred.”
The paper relies on this without support.
At 7 days post-lesion, microglia are highly responsive and the lesion is transitioning from myelin debris cleanup to initial remyelination.
“We focused our analysis on 7 days post-lesion (7 dpl), a time point at which microglia are highly responsive and the lesion is undergoing a transition from myelin debris cleanup to the initial phases of remyelination (Fig 6a).”
The paper relies on this without support.
Demyelinated lesions contain a high density of activated microglia, generally in the core, where they can remove myelin debris and release factors into the lesion microenvironment.
“Demyelinated lesions contain a high density of activated microglia, generally in the core, where they can remove myelin debris and release factors into the lesion microenvironment.”
The paper relies on this without support.
In MS, infiltrating immune cells specifically target myelin and cause white matter lesions.
“In MS, infiltrating immune cells specifically target myelin and cause white matter lesions.”
The paper relies on this without support.
Microglia migrate, grow, and proliferate in response to injury.
“Because microglia migrate, grow, and proliferate in response to injury”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These aging-related cell states exhibit upregulation of genes (e.g., B2m and Trem2 in Micro-3, Xdh in Endo-3, and Gfap and C4b in Astro-2) (Figure 2C) that have been previously shown to be enriched in microglia, endothelial cells, and astrocytes activated by inflammation and/or aging.”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Previous transcriptomic studies have revealed widespread changes in cell state in specific cell types with age, with many of these studies highlighting a role for increased inflammation as a key aspect of brain aging.17–20,25–30”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglial and astrocytic activation has also been reported in aged rodent and human brains”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For microglia and astrocytes, we observed that the genes highly upregulated with age overlapped substantially with genes that have been previously reported as being upregulated in the activated (or “reactive”) state of these cell types (e.g., Gfap and C4b for astrocytes; B2m and Lyz2 for microglia)”
From Molecular and spatial signatures of mouse brain aging at single-cell resolution (2023) · cites this paper as [29]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent progress in single-cell deep sequencing methods allowed for more refined differentiation and revealed regional-, age- and sex-dependent differences of the microglial population, and a growing number of studies demonstrate various expression profiles defining microglial subpopulations.”
From Beyond Activation: Characterizing Microglial Functional Phenotypes (2021) · cites this paper as [102]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent experiments using deep sequencing revealed differences not only depending on the brain region, but also on age, gender, and pathology [28,39,99,102,108,109].”
From Beyond Activation: Characterizing Microglial Functional Phenotypes (2021) · cites this paper as [102]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“IFN signalling, assessed by nuclear phospho-STAT1, was only active at 7 dpl in vivo and was selective to 58 ± 7% of PU.1+ nuclei (Fig. 3N,O), consistent with the largest microglia subpopulation in this model having an interferon signature 16.”
From Central nervous system regeneration is driven by microglia necroptosis and repopulation (2019) · cites this paper as [16]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The presence of a type I IFN signature in brain cells, in particular in microglia, is increasingly being associated with ageing and neurodegenerative disease in various species13,15,39,44–50.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, our dataset and others have reported a minimal effect of sex even in young adult cells (8 weeks)16,20.”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [20]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“While a previous study reported that in a model of demyelination, proliferative microglia cluster as a population (Birc5+) independent of other pathological microglia in single-cell RNA sequencing (scRNA-seq) (67)”
From Arresting the bad seed: HDAC3 regulates proliferation of different microglia after ischemic stroke (2024) · cites this paper as [67]
The cited source says what the claim attributes to it.
In the citing paper
“Previously, we optimized a cold mechanical dissociation protocol to isolate microglia for scRNA-seq with minimal ex vivo transcriptional alterations15.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“In line with our previous work15, we find that adult microglia are largely homogenous.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“inflammatory cytokines have been seen previously in a sub-set of microglia in aged C57BL/6 mice”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as Hammond et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“We plotted markers associated with microglia in the developing mouse brain from Hammond et al. 2018 [22] and found that most markers of developmental diversity are robustly expressed across all clusters rather than in a cluster-specific fashion, except macrophage cluster (cluster 0) and proliferative cluster (cluster 6) (Fig. 1D).”
From Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro (2022) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“both the activated and the interferon-related cluster increased expression of genes upregulated in injury response microglia seen following focal demyelination from lysolecithin injection [22]”
From Culture shock: microglial heterogeneity, activation, and disrupted single-cell microglial networks in vitro (2022) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, the microglia population is highly heterogeneous, comprised of cells in discrete transcriptional dynamic “substates” that appear in defined contexts and brain regions [333,334,335,336].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [335]
The cited source says what the claim attributes to it.
In the citing paper
“In addition, microglial functions vary across different ages, disease pathologies, and between sexes10–16.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“we quantified the expression levels of a marker for activated/disease-associated microglia [53, 55, 98, 99] (Cd9) and a marker for homeostatic microglia [53–57, 100–105] (Cx3cr1)”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [100]
In the citing paper
“Single cell RNA sequencing has been particularly useful, with at least 9 distinct microglial signatures identified with varying predominance, depending on the health status of the neuronal tissue [73,74].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [73]
In the citing paper
“Single-cell transcriptomic studies reveal a relatively homogeneous adult microglia population, and greater heterogeneity of microglia states at different developmental stages, during aging and in pathological conditions (Hammond et al., 2019; Li et al., 2019; Masuda et al., 2019).”
From What is a cell type and how to define it? (2022) · cites this paper as Hammond et al., 2019
In the citing paper
“Differences in gene expression profiles of different microglial populations have been recently described using single cell RNA-seq showing some microglial populations are selectively dependent on Trem2 (58–62).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [62]
In the citing paper
“A distinct subpopulation of microglia that reside in white matter (Hammond et al., 2019) are selectively activated by systemic insults such as exposure to the chemotherapy drug methotrexate (Gibson et al., 2019).”
From Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation (2022) · cites this paper as Hammond et al., 2019
In the citing paper
“The overlapping phenotypes of reactive and senescent microglia together with the heterogeneity of microglial phenotypes described in aging and disease [45,46] present a nuanced challenge to defining senescent microglia and parsing out their contribution to dysfunction.”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [45]
In the citing paper
“However, in a reactionary or dystrophic state, microglia also contribute to the pathogenesis of various NDs and post-TBI syndromes [43–45].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [45]
In the citing paper
“For example, a study by Hammond et al. compared microglia from developing, aged, and mice injured from a focal white matter injury and identified two populations highly concentrated in aged mice – one defined by Ccl4, and another enriched in several interferon-response genes [45]. In addition, a cluster predominantly in injured mice characterized by Ifi27l2a was also identified [45].”
From Untangling senescent and damage‐associated microglia in the aging and diseased brain (2023) · cites this paper as [45]
In the citing paper
“TMEM119 has been shown to be stably and selectively expressed in adult microglia (9, 95)”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [95]
In the citing paper
“Several publications within the last 2 years have begun to employ scRNAseq and mass cytometry of microglia and other CNS immune cells as ways to understand (i) global alterations in immunological gene expression and (ii) dynamic changes in immune cell-type abundance as a function of brain anatomy, aging, and neurodegeneration (87, 95, 107, 108).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [95]
In the citing paper
“Differentially expressed genes between states included the hyaluronan receptor Lyve1 (Jordão et al., 2019a; Lim et al., 2018); Spp1, a potential regulator of phagocytosis in the brain (Hammond et al., 2019); Slc40a1, an iron transporter; and Spic, which marks red pulp macrophages (Haldar et al., 2014) and bone marrow macrophages (Kohyama et al., 2009) that we confirmed by IHC (Figure 5C, S5C).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Hammond et al., 2019
In the citing paper
“and were Sall1 negative (Hammond et al., 2019).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Hammond et al., 2019
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Fiji: an open-source platform for biological-image analysis
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Integrating single-cell transcriptomic data across different conditions, technologies, and species
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Glutamate neurotoxicity and diseases of the nervous system
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Neurotoxic reactive astrocytes are induced by activated microglia
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Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
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Macrophage activation and polarization: nomenclature and experimental guidelines
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Flagged first, then by citations
Cited by
Sorted by citations
Microglia states and nomenclature: A field at its crossroads
Paolicelli, R. C., Sierra, A., Stevens, B., Tremblay, M.-E., Aguzzi, A., Ajami, B., Amit, I., Audinat, E., Bechmann, I., Bennett, M., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.020 · Cited by 1,973
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“…in aging40, ALS41, and AD42, and of microglia subpopulations recently identified in development, aging and disease, including “disease-associated microglia” (DAM)12, “neurodegenerative microglia” (MGnD)11, and microglia clusters revealed by Li et al. (2019) and Hammond et al. (2019)14, 15.”
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Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
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Metadata
- Authors
- Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., Macosko, E., Franklin, R. J. M., Piao, X., McCarroll, S., & Stevens, B.
- Affiliations
- Broad Institute (US)
- Boston Children's Hospital (US)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Corresponding author
- Stevens, Beth
- ORCID
- Venue
- Immunity
- Publisher
- openRxiv
- Published
- 2018-08-31
- Volume
- 50
- Issue
- 1
- Pages
- 253-271.e6
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6655561
- OpenAlex
- W2901838561
- Cited by
- 2,225
- References
- 83
- Citations by year
- 2026: 257 · 2025: 312 · 2024: 304 · 2023: 343 · 2022: 351 · 2021: 308 · 2020: 218 · 2019: 123 · 2018: 4
- FWCI
- 72.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Immunity (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Howard Hughes Medical Institute
- Simons Foundation
- International Rett Syndrome Foundation
- Simons Foundation Autism Research Initiative
- Rosetrees Trust
- Lundbeckfonden (R182-2014-2844)
- Stanley Center for Psychiatric Research, Broad Institute
- Medical Research Council (MC_PC_12009)
- National Institute of Mental Health (P50MH112491)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- microglia, microglial heterogeneity, microglial states, brain aging, brain injury, multiple sclerosis, reactive microglia, microglial development, single-cell RNA sequencing
- MeSH terms
- Adaptation, Physiological, Aging, Animals, Brain, Brain Injuries, Cell Differentiation, Demyelinating Diseases, Humans, Longevity, Mice, Inbred C57BL, Multiple Sclerosis, Sequence Analysis, RNA, Microglia, Mice, Single-Cell Analysis
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