The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index; 49 of the 58 sources its claims cite were checked for support.
An environment-dependent transcriptional network specifies human microglia identity
Open accessAbstract
Of mice and men's microglia: Microglia are immune system cells that function in protecting and maintaining the brain. Gosselin et al. examined the epigenetics and RNA transcripts from single microglial cells and observed consistent profiles among samples despite differences in age, sex, and diagnosis. Mouse and human microglia demonstrated similar microglia-specific gene expression profiles, as well as a shared environmental response among microglia collected either immediately after surgery (ex vivo) or after culturing (in vitro). Interestingly, those genes exhibiting differences in expression between humans and mice or after culturing were often implicated in neurodegenerative diseases. Science , this issue p. eaal3222
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
The study maps transcriptomes and regulatory landscapes of human microglia ex vivo and after culture, showing that brain environment maintains a large microglia-specific expression program. It also finds broad conservation with mouse microglia alongside species-biased genes and disease-risk gene expression.
Key findings
- From 19 surgical samples, a human microglia signature of 881 transcripts was defined as >10-fold higher than cortex at FDR 0.05; intersecting with 46 public disease datasets showed significant enrichment/depletion in 28, including AD, FTLD, HAND, schizophrenia, and Parkinson’s.
- Disease risk genes were often microglia-preferential: 28/48 AD genes, 48/81 MS genes, and about one-third of PD and schizophrenia genes.
- Human and mouse microglia transcriptomes correlated at r=0.806; 13,253/15,768 ortholog pairs were within 4-fold, while 400 human- and 293 mouse-biased mRNAs differed >10-fold at FDR 0.05. Mouse microglia signature had 900 genes >10-fold over other macrophages; ~53% (477/900) had comparable human expression.
- Culture caused rapid remodeling: >300 genes induced and >700 repressed >10-fold; at 2-fold, 2,263 up and 3,702 down. 33% of conserved signature and 31% of AD-risk genes fell >2-fold; 424/740 ex vivo super-enhancers were lost and 541 gained. TGF-β1 restored >2-fold expression of 429 of 2,398 culture-down genes.
Methods
- Microglia isolated from resected brain tissue of 19 individuals (epilepsy, tumors, acute ischemia), purified by FACS as live CD11b+CD45LowCD64+CX3CR1High; mouse C57BL/6 microglia as CD11b+CD45Low. Samples analyzed ex vivo and after 6h, 24h, or 7d culture.
- RNA-seq, ATAC-seq, and ChIP-seq for H3K4me2, H3K27ac, and PU.1; analyses included differential expression, motif enrichment, super-enhancer identification, ortholog mapping, and comparisons with cortex, public disease datasets, mouse macrophages, and developmental microglia.
Limitations
- The authors note that more individuals are needed to link genetic variation to expression, that the full set of brain-derived maintenance signals is unknown, and that culture and current iPSC-derived microglia-like cells do not preserve the ex vivo phenotype; TGF-β1 effects were modest.
- The text also makes evident limitations: samples came from heterogeneous surgical indications (epilepsy, tumor, ischemia), human macrophage RNA-seq datasets were insufficient to build a matched human microglia-specific signature, and analyses of sex differences were mostly limited to X/Y-linked genes.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
49 of 58 cited sources checked · 28 supported · 1 flagged · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“We then intersected this gene list with 46 publicly available data sets for differentially regulated genes in neurodegenerative and behavioral disorders derived from microarray or RNA-seq analysis of intact tissue (39–53). Two-sided Fisher’s exact tests revealed significant enrichment or depletion of microglia signature genes in 28 of the 46 data sets (Table S3).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
What the sources say
- Supportedcites [39] Avramopoulos D Szymanski M Wang R Bassett S Gene expression reveals overlap between normal aging and Alzheimer's disease genes Neurobiol Aging 32 2319 e2327 2334 2011 PMC2945399 20570407 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [40] Blalock EM Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses Proc Natl Acad Sci U S A 101 2173 2178 2004 14769913 PMC357071 source
- Supportedcites [41] Capurro A Bodea LG Schaefer P Luthi-Carter R Perreau VM Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis Front Neurosci 8 441 2014 25620908 PMC4288238 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [42] Colangelo V Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling J Neurosci Res 70 462 473 2002 12391607 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [43] Liang WS Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set Physiol Genomics 33 240 256 2008 18270320 PMC2826117 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Disputedcites [44] McClintick JN Ethanol treatment of lymphoblastoid cell lines from alcoholics and non-alcoholics causes many subtle changes in gene expression Alcohol 48 603 610 2014 25129674 PMC4730944 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
- Not checked — no full text of the sourcecites [45] Mishra M Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions Acta Neuropathol 114 81 94 2007 17569064 source
- Supportedcites [46] Satoh J Yamamoto Y Asahina N Kitano S Kino Y RNA-Seq data mining: downregulation of NeuroD6 serves as a possible biomarker for alzheimer's disease brains Dis Markers 2014 123165 2014 25548427 PMC4274867 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [47] Webster JA Genetic control of human brain transcript expression in Alzheimer disease Am J Hum Genet 84 445 458 2009 19361613 PMC2667989 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [48] Borjabad A Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders PLoS Pathog 7 e1002213 2011 21909266 PMC3164642 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Microglia also express hundreds of genes at higher levels than other macrophage subsets (24–26) that may be influenced by factors present in the CNS microenvironment (25, 27), suggesting mechanisms by which the brain environment influences the activity and functions of one of its primary support cells.”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Partly supportedcites [24] Gautier EL Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages Nat Immunol 13 1118 1128 2012 23023392 PMC3558276 sourceExperimental — accuracy not yet measured
The Results section, “Distinct molecular signatures among tissue macrophages” (page unavailable), reports hundreds of transcripts selectively increased or decreased in one of four macrophage populations. It specifically says microglia had *low* expression of hundreds of transcripts expressed in other populations; it does not establish that microglia expressed hundreds at higher levels. (LLM, conf=0.84)
- Supportedcites [25] Gosselin D Environment drives selection and function of enhancers controlling tissue-specific macrophage identities Cell 159 1327 1340 2014 25480297 PMC4364385 source
In Results (‘Environment-specific gene expression’), the paper reports 809 genes expressed more than 16-fold higher in microglia than in large peritoneal macrophages. It also reports that microglia differ substantially from the other macrophage subsets examined, supporting the citing sentence’s summary. (LLM, conf=0.90)
- Partly supportedcites [26] Lavin Y Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment Cell 159 1312 1326 2014 25480296 PMC4437213 sourceExperimental — accuracy not yet measured
The Results section on gene expression reports 3,348 genes differentially expressed among the sampled macrophage populations and monocytes, and identifies genes specific to microglia. It does not establish that hundreds of those genes are expressed at higher levels in microglia than in other macrophage subsets; the 3,348 figure applies across populations. (LLM, conf=0.82)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Microglia also express hundreds of genes at higher levels than other macrophage subsets (24–26) that may be influenced by factors present in the CNS microenvironment (25, 27), suggesting mechanisms by which the brain environment influences the activity and functions of one of its primary support cells.”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Supportedcites [25] Gosselin D Environment drives selection and function of enhancers controlling tissue-specific macrophage identities Cell 159 1327 1340 2014 25480297 PMC4364385 source
The Results section (“Environment-specific gene expression”) reports substantial differences between microglial and other macrophage gene expression and concludes that environment has a strong role in determining macrophage gene expression. The Discussion (“Tuning enhancer landscapes and gene expression to context-specific functions”) links the distinctive microglial phenotype to the brain environment, supporting the claim’s cautious wording. (LLM, conf=0.93)
- Supportedcites [27] Butovsky O Identification of a unique TGF-beta-dependent molecular and functional signature in microglia Nat Neurosci 17 131 143 2014 24316888 PMC4066672 source
The Results section reports that adding TGF-β1 to cultured microglia increased expression of 60 microglial genes relative to MCSF alone. It also reports reduced expression of microglial genes in mice lacking CNS TGF-β1, supporting the claim that factors in the CNS environment may influence microglial gene expression. Page numbers are not available in our copy. (LLM, conf=0.93)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We compared the levels of mRNA transcripts in C57BL/6 microglia with different resident tissue macrophage populations (26, 56) and observed 900 mRNAs with levels of expression in microglia that were 10-fold greater than the integrated mean of expression levels in the other macrophage subsets at a FDR of 0.05 (Fig. 2B).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
What the sources say
- Supportedcites [26] Lavin Y Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment Cell 159 1312 1326 2014 25480296 PMC4437213 source
The Results section, “Tissue-Resident Macrophages Can Be Distinguished by Their Gene Expression Patterns,” compares gene expression in brain microglia with other tissue-resident macrophage populations. The citing authors report the 900-mRNA result as their own finding (Fig. 2B), not as a result attributed to this source. (LLM, conf=0.92)
- Supportedcites [56] Mass E Specification of tissue-resident macrophages during organogenesis Science 353 2016 PMC5066309 27492475 source
The citation follows the mention of resident tissue macrophage populations; the 900-mRNA result is presented as the citing authors’ own observation. In “Early specification of tissue-resident macrophages,” the source compares postnatal microglia with kidney macrophages, Langerhans cells, alveolar macrophages, and Kupffer cells using bulk RNA-seq, supporting its use for that comparison. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Microglial enhancers are primed by relatively simple combinations of LDTFs (31, 32) to become sites of activity of broadly expressed signal-dependent transcription factors (SDTFs).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Partly supportedcites [31] Heinz S Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities Molecular cell 38 576 589 2010 20513432 PMC2898526 sourceExperimental — accuracy not yet measured
The Discussion describes small sets of lineage-determining factors priming regulatory elements for subsequent binding by signaling-activated factors. But the paper establishes this model in macrophages and B cells, not specifically in microglia; the microglial claim extends it to a different cell type. (LLM, conf=0.87)
- Partly supportedcites [32] Heinz S Effect of natural genetic variation on enhancer selection and function Nature 503 487 492 2013 24121437 PMC3994126 sourceExperimental — accuracy not yet measured
The Abstract and Discussion support a model in which small sets of lineage-determining transcription factors select or prime enhancers and facilitate binding by signal-dependent factors. The study tests this in mouse macrophages, not microglia, so it does not directly establish the claim about microglial enhancers. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Integration of these findings with recent studies of yolk sac and embryonic microglia (56, 63) suggests a model by which intersecting developmentally determined and environment-dependent transcriptional networks establish microglia identity and function (Fig. 6E).”
§ An environment-dependent transcriptional network specifies human microglia identity > Discussion
What the sources say
- Partly supportedcites [56] Mass E Specification of tissue-resident macrophages during organogenesis Science 353 2016 PMC5066309 27492475 sourceExperimental — accuracy not yet measured
The sections on early specification and tissue-specific transcriptional regulators show that microglial gene signatures emerge during embryonic development and that macrophage diversification follows tissue colonization. The Conclusions describe tissue-specific regulators as potentially controlling differentiation, maintenance, and function, but the paper does not establish that intersecting developmental and environment-dependent networks determine microglial identity and function; the citing sentence presents that as its own proposed model. No page numbers are available in our copy. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [63] Matcovitch-Natan O Microglia development follows a stepwise program to regulate brain homeostasis Science 353 aad8670 2016 27338705 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“which is necessary for maintenance of the in vivo mouse microglia phenotype (27, 64).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
What the sources say
- Supportedcites [27] Butovsky O Identification of a unique TGF-beta-dependent molecular and functional signature in microglia Nat Neurosci 17 131 143 2014 24316888 PMC4066672 source
The Results section, “TGF-β plays a critical role in microglia development in vivo” (page unavailable), reports loss of microglia and altered microglial morphology in adult mice lacking CNS TGF-β1. The Discussion also identifies TGF-β1 as a major microglial differentiation factor in vivo. These findings support the claim that TGF-β1 is necessary for the in vivo mouse microglial phenotype. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [64] Buttgereit A Sall1 is a transcriptional regulator defining microglia identity and function Nat Immunol 2016 27776109 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
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
“Using a stringent cutoff of 10-fold increased expression relative to cortex tissue at a false discovery rate (FDR) of 0.05, we defined a microglial gene signature in the human brain comprising 881 transcripts (Fig. 1A, Table S2).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Human microglia isolated from surgically resected brain tissue of patients with epilepsy, brain tumors, or acute ischemic events are representative of normal human microglia.
- Rests on an assumption: The ex vivo isolation procedure, including Percoll gradient centrifugation and FACS purification, does not substantially alter the microglial transcriptome.
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 ontology analysis of this extended microglia gene signature returned significant functional enrichment for CNS-related categories such as regulation of neurogenesis, synaptic signaling, CNS development, response to transforming growth factor beta (TGF-β), and regulation of neurotransmitter transport (Fig. 2C).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“For MS, 48 of 81 genes associated with risk alleles were preferentially expressed in microglia (Fig. S5).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 15
- It may state two separate claims as one. 38
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Microglia are the resident macrophage population of the central nervous system (CNS) that perform functions required for typical development, as well as homeostasis, plasticity, immunity and repair (1–5).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Rivest S Regulation of innate immune responses in the brain Nat Rev Immunol 9 429 439 2009 19461673 source
- Partly supportedcites [2] Katsumoto A Lu H Miranda AS Ransohoff RM Ontogeny and functions of central nervous system macrophages J Immunol 193 2615 2621 2014 25193935 PMC4157312 sourceExperimental — accuracy not yet measured
The Introduction identifies microglia as resident CNS phagocytes, and “Microglial functions in the CNS” describes their roles in development, homeostasis and immunity. The neurogenesis and synapse sections support a role in plasticity. The paper describes responses to injury and possible protective functions, but the passages do not establish that microglia perform functions required for repair. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [3] Shemer A Erny D Jung S Prinz M Microglia Plasticity During Health and Disease: An Immunological Perspective Trends Immunol 36 614 624 2015 26431939 source
- Supportedcites [4] Schafer DP Stevens B Microglia Function in Central Nervous System Development and Plasticity Cold Spring Harb Perspect Biol 7 a020545 2015 26187728 PMC4588063 source
The Abstract identifies microglia as resident myeloid-derived CNS cells and describes their roles in development, maintenance, plasticity, homeostatic function, and immune surveillance. The “Spatial Patterning in the Developing and Mature CNS” section also describes their response to injury, including clearance of dead cells and debris, supporting the sentence’s broad reference to repair. Our copy provides no page numbers for these passages. (LLM, conf=0.86)
- Partly supportedcites [5] Casano AM Peri F Microglia: multitasking specialists of the brain Dev Cell 32 469 477 2015 25710533 sourceExperimental — accuracy not yet measured
The review’s opening passages identify microglia as brain-resident macrophages involved in development, homeostasis, and immune protection. Its “Synaptic Refinement” discussion supports a role in neuronal remodeling, consistent with plasticity. The Conclusions describe microglial responses to injured axons, but the passages found do not establish that microglia perform functions required for repair. (LLM, conf=0.83)
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.
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Characterization of the microglia transcriptome, in conjunction with parallel whole brain cortical gene expression profiling, also enabled evaluation of the relative expression levels of genes associated with AD, PD, multiple sclerosis (MS) and Scz risk alleles (54). Many of these genes were preferentially expressed in microglia, with the relative proportion varying by disorder (Fig. 1D and Fig. S”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
What the sources say
- Could not verifycites [54] Welter D The NHGRI GWAS Catalog, a curated resource of SNP-trait associations Nucleic acids research 42 D1001 1006 2014 24316577 PMC3965119 sourceExperimental — accuracy not yet measured
The Introduction describes GWAS identification of SNP–trait associations, and Data Access gives Alzheimer’s disease as an example of a searchable trait. Neither section reports microglial expression or compares the proportion of preferentially expressed genes across disorders. The citation appears after the preceding sentence about risk alleles, not after the citing authors’ expression finding. (LLM, conf=0.78)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Within cell-specific enhancers, DNA sequences provide information about the identities of key LDTFs and the activity states of signaling pathways that control the functions of SDTFs (31, 33–35).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Partly supportedcites [31] Heinz S Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities Molecular cell 38 576 589 2010 20513432 PMC2898526 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [33] Kaikkonen MU Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription Molecular cell 51 310 325 2013 23932714 PMC3779836 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [34] C. Roadmap Epigenomics et al Integrative analysis of 111 reference human epigenomes Nature 518 317 330 2015 25693563 PMC4530010 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [35] Romanoski CE Glass CK Stunnenberg HG Wilson L Almouzni G Epigenomics: Roadmap for regulation Nature 518 314 316 2015 25693562 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Studies in mice indicate that microglia are derived from yolk sac progenitor cells that populate the brain early in development (18, 19).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Supportedcites [18] Ginhoux F Fate mapping analysis reveals that adult microglia derive from primitive macrophages Science 330 841 845 2010 20966214 PMC3719181 source
The paper reports that adult microglia derive from primitive myeloid progenitors in mice. Its fate-mapping results link microglia to yolk sac macrophages, and it reports that yolk sac progenitors migrate into the brain between embryonic days E8.5 and E9.5 (passages 5 and 7). (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [19] Schulz C A lineage of myeloid cells independent of Myb and hematopoietic stem cells Science 336 86 90 2012 22442384 source
Strength:hedged· 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, the locations and sequence content of enhancers provide insights into how non-coding genetic variation may affect gene expression and cellular phenotypes (32, 36–38).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Supportedcites [32] Heinz S Effect of natural genetic variation on enhancer selection and function Nature 503 487 492 2013 24121437 PMC3994126 source
The Abstract reports that sequence variation affects enhancer-like regions and transcriptional outcomes, and proposes using genomic data to prioritize disease-associated regulatory variants. The Direct effects of genetic variation section links mutations in enhancer-associated motifs to differences in transcription-factor binding. Together, these passages support the claim that enhancer location and sequence offer insights into how non-coding variation may affect expression and phenotypes. (LLM, conf=0.91)
- Supportedcites [36] Kasowski M Extensive variation in chromatin states across humans Science 342 750 752 2013 24136358 PMC4075767 source
The passages labeled Abstract link sequence changes in transcription-factor binding motifs to enhancer chromatin variation and report enrichment of variable regions for expression QTLs and GWAS variants. The paper also concludes that enhancers may contribute to phenotypic differences. These findings support the claim’s qualified statement that enhancer locations and sequence content provide insights into possible effects on expression and phenotypes. (LLM, conf=0.88)
- Supportedcites [37] McVicker G Identification of genetic variants that affect histone modifications in human cells Science 342 747 749 2013 24136359 PMC3947669 source
The indexed text (section labeled Abstract; no page supplied) links variants at distal regulatory sites to changes in promoter chromatin and gene expression. It also reports that sequence polymorphisms in transcription-factor binding sites are associated with changes in histone marks, supporting the claim that enhancer location and sequence offer insight into effects on cellular chromatin features. (LLM, conf=0.88)
- Partly supportedcites [38] Kilpinen H Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription Science 342 744 747 2013 24136355 PMC5502466 sourceExperimental — accuracy not yet measured
In the indexed text (section labelled Abstract; page unavailable), the paper links sequence variation and transcription-factor binding to gene expression and discusses the distribution of enhancer-activity marks. It does not establish that enhancer locations and sequence content provide insight into effects on cellular phenotypes; its measured outcomes are molecular phenotypes. (LLM, conf=0.83)
Strength:plain· 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Dysregulation of microglia functions contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD) (6–8), Parkinson’s disease (PD) (9–12) and Huntington’s disease (HD) (13–15).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Supportedcites [6] Malm TM Jay TR Landreth GE The evolving biology of microglia in Alzheimer's disease Neurotherapeutics 12 81 93 2015 25404051 PMC4322081 source
The citation to this paper falls in the Alzheimer’s disease (AD) citation group; separate citations follow the Parkinson’s and Huntington’s disease claims. The Conclusions state that microglial dysfunction is largely responsible for the inflammatory milieu in AD, and the section on neuronal function describes how disrupted microglial activity can contribute to neuronal loss. (LLM, conf=0.92)
- Supportedcites [7] Derecki NC Katzmarski N Kipnis J Meyer-Luehmann M Microglia as a critical player in both developmental and late-life CNS pathologies Acta Neuropathol 128 333 345 2014 25056803 PMC4131160 source
The citation is attached to the Alzheimer’s disease portion of the sentence. In “Developmental and age-related CNS pathologies: is microglia dysfunction a common element?”, the review describes microglial dysfunction as a contributing factor in Alzheimer’s disease and reports reduced microglial Aβ clearance during disease progression. The Parkinson’s and Huntington’s disease portions have separate citation groups and are not assessed against this source. (LLM, conf=0.90)
- Supportedcites [8] Mosher KI Wyss-Coray T Microglial dysfunction in brain aging and Alzheimer's disease Biochem Pharmacol 88 594 604 2014 24445162 PMC3972294 source
The citation attached to Alzheimer’s disease is offered for the AD portion of the sentence; separate citations follow Parkinson’s and Huntington’s disease. Section 2 describes dysfunctional microglial responses that may contribute to neurodegeneration and characterizes AD as a possible exaggerated state of microglial dysfunction. The Conclusion likewise links dysfunctional microglia to neurodegeneration and, in some cases, AD progression. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [9] Hirsch EC Vyas S Hunot S Neuroinflammation in Parkinson's disease Parkinsonism Relat Disord 18 Suppl 1 S210 212 2012 22166438 source
- Partly supportedcites [10] Croisier E Moran LB Dexter DT Pearce RK Graeber MB Microglial inflammation in the parkinsonian substantia nigra: relationship to alpha-synuclein deposition J Neuroinflammation 2 14 2005 15935098 PMC1177985 sourceExperimental — accuracy not yet measured
The citation is attached to the Parkinson’s disease portion of the sentence, not the Alzheimer’s or Huntington’s disease portions. The Discussion reports microglial activation in Parkinson’s disease and notes that inhibiting it was neuroprotective in some models, but says its pathogenetic role remains unclear. It does not establish the claimed contribution to pathogenesis. (LLM, conf=0.88)
- Supportedcites [11] Collins LM Toulouse A Connor TJ Nolan YM Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease Neuropharmacology 62 2154 2168 2012 22361232 source
This source is cited for the Parkinson’s disease portion of the sentence, not the Alzheimer’s or Huntington’s disease portions. Section 2, “Neuroinflammation in Parkinson’s disease,” states that chronic microglial activation contributes to neuronal death in PD. (LLM, conf=0.93)
- Supportedcites [12] Saijo K A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death Cell 137 47 59 2009 19345186 PMC2754279 source
This source supports the Parkinson’s disease portion of the citing sentence, to which its citation is attached. The Introduction describes evidence that inflammatory mediators from microglia modulate PD progression, and the Discussion reports that reduced Nurr1 expression in microglia and astrocytes increased inflammatory mediators and accelerated dopaminergic neuron loss in an experimental model. The paper does not establish that inflammation initiates PD in humans, but the citing sentence does not make that narrower claim. (LLM, conf=0.88)
- Supportedcites [13] Crotti A Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors Nat Neurosci 2014 PMC4113004 24584051 source
The cited paper supports the Huntington’s disease portion of the sentence; separate citations are attached to Alzheimer’s and Parkinson’s disease. In the Discussion, it reports that microglial activation in HD can promote neuronal degeneration and potentially contribute to disease pathogenesis. (LLM, conf=0.92)
- Partly supportedcites [14] Politis M Microglial activation in regions related to cognitive function predicts disease onset in Huntington's disease: a multimodal imaging study Hum Brain Mapp 32 258 270 2011 21229614 PMC6870088 sourceExperimental — accuracy not yet measured
The citation is attached to the Huntington’s disease portion of the sentence, not the Alzheimer’s or Parkinson’s disease portions. In “Activated Microglia,” the paper links microglial activation to HD severity and predicted onset, but describes its role in pathogenesis as possible rather than established. The citing sentence states that contribution more definitively. (LLM, conf=0.86)
- Partly supportedcites [15] Tai YF Microglial activation in presymptomatic Huntington's disease gene carriers Brain 130 1759 1766 2007 17400599 sourceExperimental — accuracy not yet measured
The citation to this paper is attached to Huntington’s disease, not the Alzheimer’s or Parkinson’s disease portions of the sentence. The Discussion (p. 5) says microglial activation may contribute to neuronal death in HD, but explicitly says the study demonstrated an association rather than a causal relationship; the citing sentence presents contribution as established. (LLM, conf=0.87)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This definition captures a mouse microglia gene signature set that is larger but mostly inclusive of previously described microglia signature sets (27, 57, 58).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
What the sources say
- Supportedcites [27] Butovsky O Identification of a unique TGF-beta-dependent molecular and functional signature in microglia Nat Neurosci 17 131 143 2014 24316888 PMC4066672 source
In Results, under “Identification of a unique microglial signature” (page unavailable), the paper identifies a gene signature in adult mouse microglia, including 1,572 enriched genes. The citation identifies one of the previously described signature sets; the comparison of its size and overlap with the citing authors’ new set is the citing authors’ assessment. (LLM, conf=0.86)
- Partly supportedcites [57] Chiu IM A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model Cell Rep 4 385 401 2013 23850290 PMC4272581 sourceExperimental — accuracy not yet measured
The Results section, “Identification of microglia-specific marker genes” (page not provided), defines mouse microglia-enriched gene sets, including 29 highly specific markers. It does not compare the size or overlap of those sets with previously described microglia signature sets, so “larger but mostly inclusive” is not supported by this source. (LLM, conf=0.84)
- Partly supportedcites [58] Hickman SE The microglial sensome revealed by direct RNA sequencing Nat Neurosci 16 1896 1905 2013 24162652 PMC3840123 sourceExperimental — accuracy not yet measured
The Results section (“Microglia vs. Macrophages”; page unavailable) identifies a distinct mouse microglial gene signature, supporting this paper as an example of a previously described set. It does not establish that the citing paper’s set is larger than, or mostly inclusive of, that signature. (LLM, conf=0.84)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Common SEs were associated with genes that are known to play essential roles in the development and function of virtually all macrophages whereas mouse microglia-specific SEs were associated with genes known to play restricted or selected roles in this cell type (25).”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
What the sources say
- Supportedcites [25] Gosselin D Environment drives selection and function of enhancers controlling tissue-specific macrophage identities Cell 159 1327 1340 2014 25480297 PMC4364385 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“In addition, microglia may play roles in neurodevelopmental and psychiatric diseases such as autism, schizophrenia (Scz) and depression (16, 17).”
§ An environment-dependent transcriptional network specifies human microglia identity > Abstract
What the sources say
- Not checked — no full text of the sourcecites [16] Bilimoria PM Stevens B Microglia function during brain development: New insights from animal models Brain Res 2014 25463024 source
- Supportedcites [17] Frick LR Williams K Pittenger C Microglial dysregulation in psychiatric disease Clin Dev Immunol 2013 608654 2013 23690824 PMC3652125 source
Section 5 describes evidence suggesting a role for microglial pathology in autism; section 4 reports microglial abnormalities in schizophrenia; and section 3 identifies microglia as possible mediators in depression. The claim’s cautious “may play roles” matches the paper’s uncertainty about whether these associations are causal. Page numbers were not supplied. (LLM, conf=0.92)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“rs6733839 is a non-coding risk allele for AD (59) that lies within an enhancer-like region approximately 25 kb upstream of the BIN1 transcriptional start site, suggesting regulatory function.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
What the sources say
- Partly supportedcites [59] Lambert JC Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease Nature genetics 45 1452 1458 2013 24162737 PMC3896259 sourceExperimental — accuracy not yet measured
Table 2 (Statistical analysis; page unavailable) identifies rs6733839 at the BIN1 locus and reports a significant association with Alzheimer’s disease risk. The cited paper does not establish that this SNP is non-coding. The enhancer-like region, distance from the transcriptional start site, and suggested regulatory function appear after citation (59) in the citing sentence, so they are not assessed as claims attributed to this source. (LLM, conf=0.84)
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. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Transcriptomic analysis of mouse microglia transferred to a tissue culture environment for 7 days documented significant changes in expression of hundreds of genes, with a preferential reduction in expression of microglia-specific genes (25).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
What the sources say
- Partly supportedcites [25] Gosselin D Environment drives selection and function of enhancers controlling tissue-specific macrophage identities Cell 159 1327 1340 2014 25480297 PMC4364385 sourceExperimental — accuracy not yet measured
The Results section, under “Tissue environment regulates collaborative and signal-dependent TF expression” (page unavailable), reports vast gene-expression changes after mouse microglia were cultured with IL-34 for seven days and says the microglia-specific expression program was preferentially lost. It does not give a count or statistical test for genes changed by that culture comparison, so the claim that hundreds changed significantly is not established by the text. (LLM, conf=0.81)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Recent studies have derived microglia like cells from human induced pluripotent stem cells (iPSCs) in a defined media that more closely resembles cerebrospinal fluid (65).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
What the sources say
- Supportedcites [65] Muffat J Efficient derivation of microglia-like cells from human pluripotent stem cells Nat Med 22 1358 1367 2016 27668937 PMC5101156 source
The Results section describes a fully defined, serum-free medium whose component concentrations were adjusted to match human cerebrospinal fluid. The Results also state that the authors used this medium to derive microglia-like cells from human ES and iPS cells. Our copy provides no page numbers for these passages. (LLM, conf=0.94)
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.
- Supported
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 dominant signature was observed for PU.1 in both species, with highly significant enrichment also observed for motifs assigned to CTCF, IRF, RUNX, MEF2, C/EBP, AP-1, SMAD and MAF factors (Fig. 3B, Fig. S10B).”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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
“Overall, the microglia transcriptome comparison between the two species revealed overall similarities in patterns of gene expression (Pearson’s r = 0.806), with the majority of orthologous genes pairs (13,253 of 15,768) expressed within a 4-fold range.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“For example, hundreds of genes in the microglia gene signature exhibited significant overlaps with sets of genes that were positively correlated with Braak stage in AD, were upregulated in frontotemporal lobar degeneration (FTLD) in frontal cortex, were upregulated in HIV-associated neurocognitive disorder (HAND) or were upregulated in Scz (Fig. 1C).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“Relative expression values for the 30 most highly expressed genes across each of the patients are illustrated in Figure 1B, indicating substantial individual variation for some transcripts.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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.
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
“When all transcripts were considered (i.e., including genes expressed at ≤ 2 log2 TPM), Pearson correlation coefficients were in the range of 0.94 to 0.98 (Fig. S3D), indicating no substantial outliers among samples.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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.
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
“An additional 35 factors were associated with SEs, some of which have been linked to functional roles in microglia, including SALL1, STAT3 and RELA (Fig. 3D).”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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 a cutoff of 10-fold difference and an FDR of 0.05, 400 orthologous mRNAs were preferentially expressed in human microglia and 293 mRNAs were more highly expressed in mouse microglia (Fig. 2A).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“Notable examples included higher expression in human microglia of regulators of the complement system (e.g., C2, C3, VSIG4, SERPING1) and genes involved in brain structure development, including SYNDIG1, GLDN, CTTNBP2, and ROBO3. In contrast, genes more highly expressed in mouse microglia included Hexb, Sparc, and Sall3.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“Comparing the expression of genes linked to human neurodegenerative and behavioral disorders, of the 39 AD-associated and expressed genes, 11 were higher in human microglia whereas three were increased in mouse microglia (Fig. 2E).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“Interestingly, of the top 25 most expressed, two genes, APOC1 and MPZL1, were essentially not expressed in C57BL/6 microglia; the expression of a third one, SORL1, was nearly 20 times lower in mouse than human (Fig. 2F).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“SPI1 (encoding PU.1) was the most highly expressed ETS domain transcription factor, and the top motifs were nearly perfect matches for its consensus recognition sequence.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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
“A small set of genes exhibited significant sex-specific differences in gene expression, and these were mostly related to X- and Y-linked genes (Fig. S4).”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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. 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
“Of the 2,398 genes downregulated > 2-fold in vitro, Tgf-β1 induced expression > 2-fold of 429, including Sall1, Tmem119, and P2ry12.”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The 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
“Similar results were observed for Pu.1 binding sites in mouse microglia.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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 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
“For the individuals with both ex vivo and in vitro samples available, gene expression within culture conditions (mean Pearson correlation = 0.95) was more correlated (p=0.008 by permutation test) than between the ex vivo and in vitro samples of the same individual (mean Pearson correlation = 0.89).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A subset of mRNAs encoding these factors was expressed in primitive macrophages and maintained high levels of expression in brain microglia (Fig. 6A).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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
“Remarkably, more than 2,000 genes were downregulated more than 4-fold at 6 h following plating, with some genes exhibiting partial recovery at the 7-day time point (Figs. 4E, S13D).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
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
“Overall, of the 31,164 ATAC-seq peaks associated with at least 16 normalized H3K27ac tags (i.e., high confidence sites), ~14% exhibited a loss of H3K27ac and ~20% a gain of H3K27ac (Fig. 5D), indicating remodeling of the regulatory landscape in vitro.”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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
“While SPI1 levels increased slightly, the majority of the mRNAs encoding transcription factors recognizing enriched motifs in microglia enhancers exhibited significant reductions in vitro.”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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
“Examining differences in ex vivo and in vitro microglia, we observe rapid and profound alterations in gene expression by 6 h, characterized by activation of genes associated with acute inflammatory responses and decreased expression of genes associated with diverse immune functions.”
§ An environment-dependent transcriptional network specifies human microglia identity > 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
“Of the non-redundant set of 291 microglia transcripts associated with differentially regulated genes in AD, PD, HAND, SCZ or FTD, 117 were downregulated in vitro whereas 29 were upregulated in vitro (Fig. 6D).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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
“with PU.1 being localized at 51.2% of ATAC-seq-defined regions of open chromatin associated with H3K4me2 and at 60.9% of regions exhibiting these features plus H3K27ac.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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
“Substantial subsets of these genes exhibit altered expression in neurodegenerative and behavioral diseases and are associated with non-coding risk variants.”
§ An environment-dependent transcriptional network specifies human microglia identity > 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
“Although most treatment conditions produced some effect on gene expression, none resulted in preservation of the ex vivo molecular phenotype (Fig. S16).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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
“Although we also observed substantial individual variation in genes linked to disease risk”
§ An environment-dependent transcriptional network specifies human microglia identity > Discussion
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.
The 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
“It has not yet been possible to maintain primary human microglia in a serum-free environment.”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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 a 2-fold cutoff, 2,263 genes were upregulated in vitro and 3,702 genes were downregulated at a FDR of 0.05.”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
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
“A similar proportion (30%) of genes associated with PD also displayed such reduction in vitro, whereas more limited changes for genes associated with MS and Scz were observed (Fig. S12).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
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 paired analysis of samples for which both ex vivo and 7-day in vitro microglia populations were obtained revealed more than 300 genes induced greater than 10-fold and more than 700 genes that were repressed more than 10-fold in vitro (FDR 0.05).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
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
“Extending this analysis, 424 of the 740 SEs defined ex vivo were lost and 541 new SEs were observed (Fig. 5E).”
§ An environment-dependent transcriptional network specifies human microglia identity > An environment-dependent transcriptional network
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 assignment of the second most enriched motif to CTCF was unexpected because CTCF is ubiquitously expressed and is thought to primarily play roles in the organization of broad domains of chromatin architecture. However, the identified motif was nearly a perfect match for the CTCF consensus recognition site, and CTCF was the only transcription factor expressed in microglia known to recognize”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
Strength:plain· 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
“On the basis of these observations, the variance in gene expression noted in these samples likely overestimates the variance in the isolation of microglia and implies a high degree of precision in the RNA-Seq data set.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
Tests✓ 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
“Isolated microglia exhibited a high degree of viability and RNA integrity.”
§ An environment-dependent transcriptional network specifies human microglia identity > Human microglia transcriptomes
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
“more individuals will be required to power analyses linking genetic variation to gene expression.”
§ An environment-dependent transcriptional network specifies human microglia identity > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. 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
“It is likely that more complex culture conditions, such as co-culture with neurons and astrocytes in three-dimensional or organoid contexts, will be required to more precisely model the in vivo phenotype.”
§ An environment-dependent transcriptional network specifies human microglia identity > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. 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
“However, as a small number of transcription factors thought to play important roles in microglia are divergently expressed, such as CIITA and RUNX2 proteins, there is also the potential for significant trans effects at the subsets of genes regulated by these factors.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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.
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
“Collectively, these findings provide evidence that the transcriptional mechanisms that control gene expression are largely conserved between human and mouse microglia and that differences in gene expression are primarily driven by species-specific organization of cis regulatory elements at target genes.”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
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
“Cultured microglia remained positive for Iba1 staining, whereas no expression of markers for astrocytes or neurons was observed, indicating that changes in RNA expression were not due to contaminating cells (Fig. S13A).”
§ An environment-dependent transcriptional network specifies human microglia identity > Alterations of the human microglia transcriptome in vitro
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
“The frequency distribution of many of these motifs is consistent with the corresponding transcription factors forming ternary complexes with PU.1 (e.g., the IRF motif, Fig. S10C) or functioning as collaborative binding partners (e.g., CTCF, AP-1 and RUNX motifs, Fig. S10C).”
§ An environment-dependent transcriptional network specifies human microglia identity > Enhancer landscape of human microglia
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Motif enrichment in open chromatin indicates binding and activity of the corresponding transcription factors.
The paper relies on this without support.
Human microglia isolated from surgically resected brain tissue of patients with epilepsy, brain tumors, or acute ischemic events are representative of normal human microglia.
“Microglia were isolated from brain tissue resected for treatment of epilepsy, brain tumors or acute ischemic events in 19 individuals.”
“As judged by neuropathological diagnostic evaluation, none of the samples displayed evidence of pathological microgliosis (i.e. loss of tiled distribution, process retraction and enlarged cell bodies) despite the occasional presence of reactive cells (Fig. S1).”
The paper relies on this without support.
The ex vivo isolation procedure, including Percoll gradient centrifugation and FACS purification, does not substantially alter the microglial transcriptome.
“A microglia-rich cell fraction was isolated by Percoll gradient centrifugation and further purified by FACS, with final gating on live-CD11b+CD45LowCD64+CX3CR1High single cells (Fig. S2A).”
“On the basis of these observations, the variance in gene expression noted in these samples likely overestimates the variance in the isolation of microglia and implies a high degree of precision in the RNA-Seq data set.”
The paper relies on this without support.
Motif enrichment in open chromatin indicates binding and activity of the corresponding transcription factors.
“De novo motif analysis of ATAC-seq peaks associated with H3K4me2 was performed to identify the most highly enriched transcription factor recognition motifs associated with poised or active chromatin.”
“The frequency distribution of many of these motifs is consistent with the corresponding transcription factors forming ternary complexes with PU.1 (e.g., the IRF motif, Fig. S10C) or functioning as collaborative binding partners (e.g., CTCF, AP-1 and RUNX motifs, Fig. S10C).”
The paper relies on this without support.
Current efforts to reprogram various starting cell populations to microglia-like cells largely achieve an in vitro phenotype.
“Importantly, current efforts to reprogram various starting cell populations to microglia-like cells largely achieve an in vitro phenotype.”
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
“ATAC-seq and H3K27ac ChIP-seq profiles generated from PU.1 nuclei were highly correlated with those previously defined in ex vivo microglia”
From Brain cell type–specific enhancer–promoter interactome maps and disease - risk association (2019) · cites this paper as [14]
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 transcriptome-wide studies of bulk ex vivo human microglia have consistently suggested that microglia change with age and have transcriptomes that are enriched for disease-related genes3–5.”
From Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease (2020) · cites this paper as [4]
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 [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
“Cluster 1 genes were enriched in genes that were downregulated in AD brain and in response to in vitro culture.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [34]
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
“P2RY12 expression is lost upon microglia activation74, culture34”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [34]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“The BIN1 microglia-specific enhancer is PLAC-linked to the BIN1 promoter (Fig. 4A), binds to PU.1 (14) and contains the AD-risk variant rs6733839, which has the second highest AD-risk score after APOE and was fine-mapped as a casual variant (Fig. 3A).”
From Brain cell type–specific enhancer–promoter interactome maps and disease - risk association (2019) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“As the tissue-resident macrophages of the brain, microglia are highly sensitive to perturbations in their environment13,14.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Previous reports comparing cell isolation protocols or cells postisolation have often focused on aspects such as cell viability and/or yield4,62 over whether the isolated cells are truly reflective of their in vivo state13,14.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [13]
The cited source says what the claim attributes to it.
In the citing paper
“Regardless of any such mechanistic heterogeneity, a common property is that the activity of individual enhancers is generally cell-type-specific or even condition-specific99, and this specificity is a function of the expression levels of the TFs that are able to bind to it89.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [99]
The cited source says what the claim attributes to it.
In the citing paper
“Cluster 2 genes were significantly enriched for genes upregulated following in vitro culture34 and in AD-derived microglia33.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [34]
The cited source says what the claim attributes to it.
In the citing paper
“Cluster 1 contained genes that were upregulated in the cortical regions compared to subcortical regions, such as P2RY12, CD36, and MRC1, and was enriched in genes that were downregulated in AD brain33 and in response to in vitro culture34.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [34]
The cited source says what the claim attributes to it.
In the citing paper
“The downregulated genes were significantly enriched for cell motility, polarity, IL-6 cytokine signaling (Fig. 3b), and for genes also downregulated following in vitro culture34 and in AD-derived microglia33 (Fig. 3c).”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [34]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Indeed, BIN1 mRNA encoding isoform 9 is highly transcribed by glial cells [21, 22].”
From BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 are implicated in tau pathology (2020) · cites this paper as [22]
Experimental — accuracy not yet measuredIn the citing paper
“These studies have largely concluded that microglia undergo the most prominent changes in diseased brains, due to a combination of increased microglia numbers along with a robust transcriptional activation signature on a per-microglia basis.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [7]
In the citing paper
“mouse and human microglia, which have recently emerged as key players in Alzheimer’s Disease and other neurodegenerative diseases, show differences in particular in the expression of disease-relevant genes19, and they adopt distinctly different states in human diseased brains compared to mouse models20.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [19]
In the citing paper
“First, there are differences between disease-relevant cell types, such as neurons and glia, between humans and mice.”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [19]
In the citing paper
“RNA-sequencing studies of human microglia isolated from non-AD brain tissue (Galatro et al., 2017; Gosselin et al., 2017) showed broad similarity with mouse microglial gene expression profiles, although there were many differences such as higher expression of the C2 and C3 complement genes in human microglia.”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Gosselin et al., 2017
In the citing paper
“Our four putative risk genes, OAS1, LAPTM5, LILRB4 and ITGAM/CD11b are expressed abundantly in the human microglia (Galatro et al., 2017; Gosselin et al., 2017)”
From Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk (2019) · cites this paper as Gosselin et al., 2017
In the citing paper
“there is a substantial overlap in human orthologues expressed by the mouse amyloid-responsive microglia and the transcripts expressed abundantly by human microglia from Galatro et al. (2017) and Gosselin et al. (2017).”
From Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk (2019) · cites this paper as Gosselin et al., 2017
In the citing paper
“a number of important studies have compared gene expression in microglia from mice and humans, and while they have shown a significant overlap between the transcriptomes of the two species, they have also seen a number of genes are expressed selectively more abundantly in human microglia”
From Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk (2019) · cites this paper as Gosselin et al., 2017
In the citing paper
“Discoveries over the last decade suggest that many, perhaps even a majority, of the genes contributing risk to AD are expressed primarily by microglia (1, 2), the resident myeloid cells of the brain parenchyma.”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [1]
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“Newly developed technics, including RNA-sequencing, epigenetic studies, bioinformatics, and quantitative proteomics helped to better understand and characterize microglial diversity in rodents and humans (Hickman et al., 2013; Gosselin et al., 2017; Butovsky and Weiner 2018; Olah et al., 2018).”
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“This is particularly problematic as transcriptomic studies have revealed significant differences in the genetic profile between rodent and human microglia [23, 24].”
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Shock and kill within the CNS: A promising HIV eradication approach?
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The role of microglia in ischemic preconditioning
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“In addition, microglia-specific genes demonstrate a high degree of overlap with genes linked to neurodegenerative conditions such as Alzheimer's disease (AD) (Gosselin et al., 2017).”
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“For example, activity-dependent regulation in neurons involves many enhancer elements 23 , while promoters regulate species-specific differences in microglial activation 24 .”
InfluentialC/EBPβ/AEP Signaling Drives Alzheimer’s Disease Pathogenesis
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Microglial heterogeneity in chronic pain
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Microglia and metastases to the central nervous system: victim, ravager, or something else?
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“…– also have anatomical, functional, morphological, and genetical differences in their astrocytes (Oberheim et al., 2009) and neurons (Kalmbach et al., 2018; Hodge et al., 2019), and to a lesser extent in oligodendrocytes/myelin (Ishii et al., 2009) and microglia (Gosselin et al., 2017).”
Background3D spatial genome organization in the nervous system: From development and plasticity to disease
Fujita, Y., Pather, S. R., Ming, G., & Song, H. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.004 · Cited by 37
Nonresolving macrophage‐mediated inflammation in malignancy
Murray, P. J. (2017) · FEBS Journal · doi:10.1111/febs.14210 · Cited by 38
Microglia in Alzheimer's Disease: A Role for Ion Channels
Thei, L., Imm, J. L., Kaisis, E., Dallas, M. L., & Kerrigan, T. L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00676 · Cited by 37
“It is only recently that a distinct transcriptomic profile of microglia has emerged (Hickman et al., 2013; Butovsky et al., 2014; Holtman et al., 2015; Bennett et al., 2016; Gosselin et al., 2017; Keren-Shaul et al., 2017; Krasemann et al., 2017).”
BackgroundCircadian modulation of microglial physiological processes and immune responses
Guzmán‐Ruiz, M. A., Guerrero‐Vargas, N. N., Lagunes‐Cruz, A., González‐González, S., García‐Aviles, J. E., Hurtado‐Alvarado, G., Méndez‐Hernández, R., Chavarría, A., Morin, J., Arriaga-Ávila, V. S., et al. (2022) · Glia · doi:10.1002/glia.24261 · Cited by 37
“…demonstrating that microglial transcriptional profiles vary depending on a wide variety of factors such as; the developmental stage, brain region, and health status of an individual (Bennett et al., 2016; Gosselin et al., 2017; Keren-Shaul et al., 2017; Li et al., 2019; Masuda et al., 2019).”
BackgroundJuul‐Madsen, K., Qvist, P., Bendtsen, K. L., Langkilde, A. E., Vestergaard, B., Howard, K. A., Dehesa-Etxebeste, M., Paludan, S. R., Andersen, G. R., Jensen, P. H., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.1900494 · Cited by 37
Tools for studying human microglia: In vitro and in vivo strategies
Warden, A. S., Han, C. Z., Hansen, E. A., Trescott, S., Nguyen, C. T., Kim, R. Y., Schafer, D. M., Johnson, A., Wright, M., Ramírez, G., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.10.008 · Cited by 38
“C Motif Chemokine Ligand/Receptor CD Cluster of differentiation receptors CEBP CCAAT/enhancer-binding protein CNS Central nervous system CO Cerebral organoid CRISPR/ Clustered regularly interspaced short palindromic repeats/ CRISPRi/a CRISPR interference/activation CSF1/CSF1R Colony stimulating factor 1/receptor CX3CR…”
BackgroundMethodResultInfluentialSelf-citationAPOE and immunity: Research highlights
Kloske, C. M., Barnum, C. J., Batista, A. F., Bradshaw, E. M., Brickman, A. M., Bu, G., Dennison, J. L., Gearon, M. D., Goate, A., Haass, C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13020 · Cited by 38
Salvermoser, J., van Blijswijk, J., Papaioannou, N. E., Rambichler, S., Pásztói, M., Pakalniškytė, D., Rogers, N. C., Keppler, S. J., Straub, T., Sousa, C. R. E., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00699 · Cited by 39
Munford, R. S., Weiss, J. P., & Lu, M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.015254 · Cited by 38
Wolf, J., Boneva, S., Rosmus, D.-D., Agostini, H. T., Schlunck, G., Wieghofer, P., Schlecht, A., & Lange, C. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.3.9 · Cited by 36
“26,27 In addition, expression levels of the most specific marker genes, known from single-cell RNA sequencing of human retinal tissue, 27 of potentially contaminating cells, such as photoreceptors, retinal ganglion cells, bipolar cells, and endothelial cells, were studied.”
InfluentialRegulation of microglia phagocytosis and potential involvement of exercise
Li, C., Wang, Y., Xing, Y., Han, J., Zhang, Y., Zhang, A., Hu, J., Hua, Y., & Bai, Y. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.953534 · Cited by 37
Microglia and modifiable life factors: Potential contributions to cognitive resilience in aging
Duggan, M. R., & Parikh, V. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113207 · Cited by 38
The origin and repopulation of microglia
Zhang, L., Cao, Y., Zhang, X., Gu, X., Mao, Y. Q., & Peng, B. (2021) · Developmental Neurobiology · doi:10.1002/dneu.22862 · Cited by 42
“These studies demonstrated that species-specific patterns of gene expression in microglia (Gosselin et al., 2017).”
BackgroundRegulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction
Breitmeyer, R., Vogel, S., Heider, J., Hartmann, S.-M., Wüst, R., Keller, A., Binner, A., Fitzgerald, J. C., Fallgatter, A. J., & Volkmer, H. (2023) · Communications Biology · doi:10.1038/s42003-023-04852-9 · Cited by 36
The role of microglia and P2X7 receptors in gliomas
Kan, L. K., Williams, D. J., Drummond, K. J., O'Brien, T. J., & Monif, M. (2019) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2019.04.010 · Cited by 37
Zheng, X., Gong, T., Tang, C., Zhong, Y., Shi, L., Fang, X., Chen, D., & Zhu, Z. (2022) · BMC Anesthesiology · doi:10.1186/s12871-022-01915-y · Cited by 35
Specialized functions of resident macrophages in brain and heart
Nicolás-Ávila, J. Á., Hidalgo, A., & Ballesteros, I. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.6mr0118-041r · Cited by 36
Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation
Žilková, M., Nölle, A., Kováčech, B., Kontseková, E., Weisová, P., Filipčík, P., Škrabana, R., Prčina, M., Hromádka, T., Cehlár, O., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00948-z · Cited by 35
Microglia in the context of multiple sclerosis
Zhang, X., Chen, F., Sun, M., Wu, N., Liu, B., Yi, X., Ge, R., & Fan, X. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1157287 · Cited by 36
de Sá, R. V., Sudrià-Lopez, E., Luna, M. C., Harschnitz, O., van den Heuvel, D. M. A., Kling, S., Vonk, D., Westeneng, H., Karst, H., Bloemenkamp, L. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-51676-0 · Cited by 37
Parajuli, B., Saito, H., Shinozaki, Y., Shigetomi, E., Miwa, H., Yoneda, S., Tanimura, M., Omachi, S., Asaki, T., Takahashi, K., et al. (2021) · Glia · doi:10.1002/glia.23985 · Cited by 35
“Various methods have been developed to induce microglia differentiation from embryonic or induced pluripotent cells (Beutner, Roy, Linnartz, Napoli, & Neumann, 2010; Brownjohn et al., 2018; Haenseler et al., 2017; Muffat et al., 2016).”
MethodMatera, A., Compagnion, A.-C., Pedicone, C., Kotah, J. M., Ivanov, A., Monsorno, K., Labouèbe, G., Leggio, L., Pereira-Iglesias, M., Beule, D., et al. (2025) · Immunity · doi:10.1016/j.immuni.2024.11.003 · Cited by 34
Veremeyko, T., Yung, A. W. Y., Dukhinova, M., Strekalova, T. V., & Ponomarev, E. D. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00453 · Cited by 35
“This process enables the binding of several key transcription factors (TFs) that mediate microglial differentiation (Gosselin et al., 2017; Holtman et al., 2017).”
BackgroundIs the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?
Salado-Manzano, C., Perpiñá, U., Straccia, M., Molina-Ruiz, F. J., Cozzi, E., Rosser, A., & Canals, J. M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00250 · Cited by 34
Zhu, K., Zhu, Y., Hou, X., Chen, W., Qu, X., Zhang, Y., Li, Z., Wang, C., Chen, J., Lv, L., et al. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.621477 · Cited by 35
The use and limitations of single‐cell mass cytometry for studying human microglia function
Fernández‐Zapata, C., Leman, J. K. H., Priller, J., & Böttcher, C. (2020) · Brain Pathology · doi:10.1111/bpa.12909 · Cited by 38
Epigenetic Regulation of Nutrient Transporters in Rheumatoid Arthritis Fibroblast‐like Synoviocytes
Torres, A., Pedersen, B., Cobo, I., Ai, R., Coras, R., Murillo‐Saich, J., Nygaard, G., Sánchez‐López, E., Murphy, A. N., Wang, W., et al. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42077 · Cited by 34
The 2022 yearbook of Neurorestoratology
Huang, H., Bach, J. R., Sharma, H. S., Saberi, H., Jeon, S. R., Guo, X., Shetty, A. K., Hawamdeh, Z. M., Sharma, A., Wild, K. V., et al. (2023) · Journal of Neurorestoratology · doi:10.1016/j.jnrt.2023.100054 · Cited by 37
Epilepsy progression is associated with cumulative DNA methylation changes in inflammatory genes
Martins-Ferreira, R., Leal, B., Chaves, J., Li, T., Ciudad, L., Rangel, R., Santos, A., da Silva, A. M., Costa, P., & Ballestar, E. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102207 · Cited by 33
Rheinberger, M., Costa, A. L., Kampmann, M., Glavaš, D., Shytaj, I. L., Sreeram, S., Penzo, C., Tibroni, N., García‐Mesa, Y., Leskov, K., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112110 · Cited by 33
Murai, N., Mitalipova, M., & Jaenisch, R. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14879 · Cited by 33
“, 2016) but is one of the genes most affected by the in vitro culture conditions (Gosselin et al., 2017).”
BackgroundParkinson’s Disease: Can Targeting Inflammation Be an Effective Neuroprotective Strategy?
Gundersen, V. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.580311 · Cited by 33
Functional microglia derived from human pluripotent stem cells empower retinal organs
Gao, M.-L., Zhang, X., Han, F., Xu, J. M., Yu, S., Jin, K., & Jin, Z. (2022) · Science China Life Sciences · doi:10.1007/s11427-021-2086-0 · Cited by 33
“Similar to a previous report of positive crosstalk between hPSC-derived microglia and iPSC-derived cortical neurons in a co-culture system (Haenseler et al., 2017), we observed more ramified hPSC-derived microglia after coculture with hROs (Figure 7).”
Resultde Soysa, Y., Therrien, M., Walker, A. C., & Stevens, B. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101651 · Cited by 34
Defining Microglial States and Nomenclature: A Roadmap to 2030Preprint
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Self-citationPramotton, F. M., Spitz, S., & Kamm, R. D. (2024) · Advanced Science · doi:10.1002/advs.202403892 · Cited by 33
Tissue-Resident Macrophage Membrane-Coated Nanomedicine for Targeted Tumor Therapy
Su, X., Su, M., Guo, E., Zhou, Y., Yang, X., Li, S., & Ye, Y. (2025) · ACS Nano · doi:10.1021/acsnano.5c04463 · Cited by 34
Gumbs, S. B. H., Kübler, R., Gharu, L., Schipper, P. J., Borst, A. L., Snijders, G. J. L., Ormel, P. R., van Berlekom, A. B., Wensing, A. M. J., de Witte, L. D., et al. (2022) · Journal of NeuroVirology · doi:10.1007/s13365-021-01049-w · Cited by 34
Berki, P., Cserép, C., Környei, Z., Pósfai, B., Szabadits, E., Domonkos, A., Kellermayer, A., Nyerges, M., Wei, X., Módy, I., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49773-1 · Cited by 35
CELF2 regulates the species-specific alternative splicing of TREM2
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Jiao, F., Li, Z., He, C., Xu, W., Yang, G., Liu, T., Shen, H., Cai, J., Anastas, J. N., Mao, Y. Q., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba2113 · Cited by 32
“However, expression of MHC class II genes has also been detected in the CNS (central nervous system), including neural stem cells (18), microglia cells (19), and IFN-–induced astrocytes (20), raising the possibility that MHC II molecules may play a role in the CNS.”
BackgroundAdvanced in vitro models: Microglia in action
Cakir, B., Kiral, F. R., & Park, I.-H. (2022) · Neuron · doi:10.1016/j.neuron.2022.10.004 · Cited by 32
Alzheimer’s in a dish – induced pluripotent stem cell-based disease modeling
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Korvatska, O., Kiianitsa, K., Ratushny, A. V., Matsushita, M. M., Beeman, N. E., Chien, W., Satoh, J., Dorschner, M. O., Keene, C. D., Bammler, T. K., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.559342 · Cited by 31
“In the brain, MICB is expressed primarily by microglia (32), and it is the most significantly upregulated gene in TREM2 R47H AD (Figure 1A).”
BackgroundUnravelling the glial response in the pathogenesis of Alzheimer's disease
Alibhai, J. D., Diack, A. B., & Manson, J. C. (2018) · The FASEB Journal · doi:10.1096/fj.201801360r · Cited by 31
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Liu, E., Karpf, L., & Bohl, D. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.767041 · Cited by 32
“Clearly, iPSC require specific environmental signals for proper differentiation and maintenance of their identity (Bohlen et al., 2017; Gosselin et al., 2017), suggesting that for ALS and FTD studies, iPS-derived microglia have to be co-cultured with either MNs or cortical neurons,…”
BackgroundMicroglia: sculptors of neuropathic pain?
Ward, H. L., & West, S. J. (2020) · Royal Society Open Science · doi:10.1098/rsos.200260 · Cited by 35
“Importantly, studies now begin to characterize single-cell molecular phenotypes and genetic landscapes of ‘activated’ microglia [84,120,121].”
BackgroundMacrophage dysfunction in cystic fibrosis: Nature or nurture?
Turton, K. B., Ingram, R. J., & Valvano, M. A. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.4ru0620-245r · Cited by 31
Microglia and its Genetics in Alzheimer's Disease
Liang, X., Wu, H., Colt, M., Guo, X., Pluimer, B. R., Zeng, J., Dong, S., & Zhao, Z. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211105140732 · Cited by 32
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease
Nott, A., & Holtman, I. R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1168539 · Cited by 33
Self-citationPatient-Derived In Vitro Models of Microglial Function and Synaptic Engulfment in Schizophrenia
Sheridan, S. D., Horng, J. E., & Perlis, R. H. (2022) · Biological Psychiatry · doi:10.1016/j.biopsych.2022.01.004 · Cited by 30
Li, Z., Chen, K., Shao, Q., Lu, H., Zhang, X., Pu, Y., Sun, X.-J., He, H., & Cao, L. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02696-y · Cited by 30
Metadata
- Authors
- Gosselin, D., Skola, D., Coufal, N. G., Holtman, I. R., Schlachetzki, J. C. M., Sajti, E., Jaeger, B. N., O’Connor, C., Fitzpatrick, C., Pasillas, M. P., Pena, M., Adair, A., Gonda, D. D., Levy, M. L., Ransohoff, R. M., Gage, F. H., & Glass, C. K.
- Affiliations
- University of California San Diego (US)
- Salk Institute for Biological Studies (US)
- University Medical Center Groningen (NL)
- Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0651, USA.
- Biogen (United States) (US)
- Corresponding author
- Gosselin, David
- Skola, Dylan
- Coufal, Nicole G.
- Holtman, Inge R.
- Schlachetzki, Johannes C. M.
- Glass, Christopher K.
- ORCID
- Venue
- Science
- Published
- 2017-06-23
- Volume
- 356
- Issue
- 6344
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5858585
- OpenAlex
- W2619332462
- Semantic Scholar
- 7b09a8c02f1443df2339a07b52615cddd29b752a
- Cited by
- 1,220
- References
- 77
- Citations by year
- 2026: 131 · 2025: 123 · 2024: 175 · 2023: 112 · 2022: 138 · 2021: 142 · 2020: 142 · 2019: 120 · 2018: 107 · 2017: 29
- FWCI
- 53.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- NIH (NS096170, GM085764)
- 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
- human microglia, transcriptional regulatory networks, epigenetic landscape, neurodegenerative diseases, behavioral disorders, non-coding variants, transcriptome, macrophage migration, CNS homeostasis
- MeSH terms
- Animals, Brain Neoplasms, Cells, Cultured, Environment, Epilepsy, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Microglia, Gene Expression Profiling, Mice, Gene Regulatory Networks
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