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A cellular and spatial map of the choroid plexus across brain ventricles and ages
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Abstract
SUMMARY The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells showed regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulated host defense programs and resident macrophages upregulated IL-1β signaling genes. Our atlas revealed cellular diversity, architecture and signaling across ventricles during development, maturation and aging of the ChP brain barrier.
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TL;DR
This paper presents a single-cell and spatial atlas of the mouse choroid plexus across lateral, third, and fourth ventricles in developing, adult, and aged brains. It identifies ventricle- and age-dependent epithelial/mesenchymal programs, a Wnt1+ common progenitor for epithelial and neuronal cells, and aging-associated immune signaling including IL-1β.
Key findings
- Profiled 15,620 single cells and 83,040 single nuclei from lateral, third, and fourth ventricle choroid plexuses of developing (E16.5, n = 13), adult (4 months, n = 4), and aging (20 months, n = 9) mice, defining major cell classes and subtypes across ages and ventricles.
- Trajectory inference and lineage tracing supported a common progenitor pool for epithelial and neuronal cells; Wnt1+ progenitors near FoxJ1+ epithelial cells gave rise to both epithelial and neuronal progeny in the 4V and 3V ChP.
- Epithelial and fibroblast cells showed ventricle-regionalized expression starting embryonically and persisting with age; maturation produced a large transcriptional shift, and aged epithelial cells upregulated host-defense programs while aged macrophages upregulated IL-1β signaling genes.
- Mesenchymal cells expressed ACE2 and accessory SARS-CoV-2 entry components, and ligand-receptor analysis predicted mesenchymal cells as an interaction hub, with IL-1β signaling from aged macrophages to endothelial and mesenchymal cells.
Methods
- Mouse ChP from LV, 3V, and 4V was dissected at E16.5, 4 months, and 20 months; embryonic samples were profiled by scRNA-seq, and all ages by snRNA-seq, followed by smFISH, immunostaining, transgenic lineage tracing, and whole-tissue imaging.
- Analyses included clustering, diffusion maps, RNA velocity, topic modeling, pseudobulk differential expression, and CellPhoneDB-based ligand-receptor interaction inference across ventricles and ages.
- Validation used marker immunostaining, RNAscope, Cx3cr1-GFP and Wnt1-CRE2::R26R-Confetti mice, electron microscopy, and published in situ hybridization data.
Limitations
- The paper states: small tissue size required pooling samples across donors, especially for immune cells; dissection purity was limited by anatomically defined borders, particularly for 3V ChP; adult/aged cellular health led to differential processing (scRNA-seq for embryonic vs. frozen samples and snRNA-seq for adult/aged, also applied to embryonic), introducing computational comparison challenges; continuous cell-state and age transitions required topic modeling; and lowly expressed genes may be missed due to coverage depth.
- Evident from the text: the atlas is mouse-only, and several conclusions about signaling and progenitor relationships rely on inferred trajectories and predicted ligand-receptor interactions, with validation focused on selected markers and lineages.
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In the paper
“In embryos, subsets of glial cells expressed markers of neural progenitor/stem-like cells (e.g. Pax6, Nes, Sox2, Rspo2/3) or of oligodendrocyte precursor cells (OPCs, e.g. Olig1, Olig2) (Kriegstein and Alvarez-Buylla, 2009) (Figure 2A, S2A,B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
What the sources say
- Not checked yetcites Kriegstein and Alvarez-Buylla, 2009 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we profiled 15,620 single cells (scRNA-seq) and 83,040 single nuclei (snRNA-seq) from the lateral (LV), third (3V), and fourth (4V) brain ventricles of developing (embryonic day [E]16.5, n = 13), adult (4 months, n = 4) and aging (20 months, n = 9) mice”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Molecular survey defines the cellular composition of the ChP across ventricles and ages
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In the paper
“We leveraged the inclusion of adjacent brain tissue in our atlas to map the boundary between the 3V ChP and developing pineal gland using published ISH (Lein et al., 2007; Visel et al., 2004) of marker genes from our data (Figure S2C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Embryonic cells partitioned into clusters identifying epithelial, mesenchymal (mural and fibroblast), endothelial, immune, neuronal and glial cells in each ChP from all ventricles (by marker genes expression, Figure 1C, S1A,B,C, Table S1, STAR Methods).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Molecular survey defines the cellular composition of the ChP across ventricles and ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The embryonic ChP scRNA-seq profiles of epithelial, glial, and neuronal cells were not discretely separable by low-dimensional embedding (Figure 1C, STAR Methods), suggesting a common progenitor pool for both epithelial and neuronal cells may exist in the ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The neuro-glial populations were proportionally low (8%/2.5% of cells/nuclei, Figure S1B,G), yet sub-clustering revealed substantial diversity within each population.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“The analysis arranged neurons and mature epithelial cells at two opposite ends of a trajectory, with a progenitor glia-like population at the node between them (Figure 2B, further supported RNA velocity (La Manno et al., 2018) analysis, Figure S2F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
What the sources say
- Not checked yetcites La Manno et al., 2018 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Two neuro-glial subsets in the 3V expressed markers of developing pinealocytes (e.g. Crx, Krt19; Figure 2A, clusters 12 and 13, Figure S2B), which develop caudal to the 3V ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
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
“Focusing on the URL, we validated that Wnt1+ cells localized near FoxJ1-expressing ChP epithelial cells (by smFISH and immunohistochemistry, Figures 2C-G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparing patterns across the three age groups using snRNA-seq data revealed all mesenchymal cell types – pericytes, fibroblasts, vSMCs, and meningeal fibroblasts (Figure 4C-F, S4G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Regionalized differences identified by scRNA-seq data (Figure 3C) were recapitulated in the corresponding embryo snRNA-seq data (Figure S3E).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Macrophage states were associated with distinct spatial niches in the ChP, either basally under the epithelial cell monolayer or on the apical surface (e.g., epiplexus position, Figure 5D), by image analysis of Cx3cr1-GFP transgenic mouse.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“4V ChP fibroblasts also expressed high levels of genes encoding signaling molecules with roles in hindbrain development (e.g., Hhip (Chuang and McMahon, 1999), Ptch1 (Huang et al., 2009), Rbp4 (Chang et al., 2016), and Wisp1 (Lun et al., 2015a, Figure 4B, S4D).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Mature epithelial cell profiles partitioned by ventricle (Figure 3A), matching differential gene expression between LV and 4V ChP by bulk RNA-seq (Lun et al., 2015b) (Figure S3A).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
- Not checked yetcites Lun et al., 2015b
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diffusion map embedding of scRNA-seq embryonic profiles showed graded gene expression patterns spanning three transcriptional states (Figure 5C, STAR Methods).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“3V ChP fibroblasts (Topic 7) shared expression signatures with meningeal fibroblasts (e.g., Apod, Slc1a3) and the ‘ceiling cell’ fibroblast subtype (e.g., Crym, Figure 4B, S4E; DeSisto et al., 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
What the sources say
- Not checked yetcites DeSisto et al., 2020 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“A subset of Slc40a1+ macrophages expressed Spic and Clec4n (Figure S5D), corresponding to recently described Clec4n+ macrophages in postnatal ChP (Li et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Li et al., 2019
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“We found age-dependent expression of transporters and channels involved in ion and water movement across the epithelium, aligning with a key function of epithelial cells to produce CSF (Damkier et al., 2013; Fame and Lehtinen, 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
- Not checked yetcites Damkier et al., 2013 source
- Not checked yetcites Fame and Lehtinen, 2020
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Mapping the expression of highly scoring genes for these topics in the 4V ChP in situ identified a rostro-caudal gradient of expression (Figure 3E), which may derive from the earliest stages of development, when roof plate progenitors originating from distinct rhombomeres give rise to hindbrain and 4V ChP (Hunter and Dymecki, 2007).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
- Not checked yetcites Hunter and Dymecki, 2007
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ventricle-dependent topics revealed regionalized expression of genes encoding growth factors (Bmp4/7, Wnt4/2) and extracellular matrix proteins (Figure 4B, S4F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In macrophages (Cx3cr1+;Csf1R+), the largest class of immune cells in the ChP, we found heterogeneity within stromal and CSF-contacting epiplexus cells.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Mesenchymal cells across all ages and ventricles expressed Ace2 (Angiotensin I converting enzyme 2; Figure 4J,S4J), the SARS-CoV-2 receptor, and other known and putative accessory components, including cathepsins (Ctsl and Ctsb (Muus et al., 2020)) and Neuropilin-1 (NRP1 (Cantuti-Castelvetri et al., 2020)) (Figure 4J, S4J).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > ACE2, the SARS-CoV-2 receptor is expressed by mesenchymal cells in the ChP
What the sources say
- Not checked yetcites Muus et al., 2020
- Not checked yetcites Cantuti-Castelvetri et al., 2020 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Differentially expressed genes between states included the hyaluronan receptor Lyve1 (Jordão et al., 2019a; Lim et al., 2018); Spp1, a potential regulator of phagocytosis in the brain (Hammond et al., 2019); Slc40a1, an iron transporter; and Spic, which marks red pulp macrophages (Haldar et al., 2014) and bone marrow macrophages (Kohyama et al., 2009) that we confirmed by IHC (Figure 5C, S5C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
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
“Topic modeling of the embryonic cells recovered topics capturing mesenchymal cell types (e.g., pericytes (topic 3), proliferating cells (topics 12 and 16)), and ventricle-dependent topics within fibroblasts (e.g., LV (Topics 8 and 18), 3V (Topics 2 and 7) and 4V (Topic 5)) (Figure 4B, S4B,C, Table S4).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The maturing ChP epithelial cells in each ventricle transiently expressed ciliogenesis genes including Ccdc67/Deup1 (Figures 2B, M-O), which drives centriole biogenesis, an essential step of multi-ciliation (Brooks and Wallingford, 2014).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
What the sources say
- Not checked yetcites Brooks and Wallingford, 2014
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, Ins2, encoding an insulin precursor and associated with Topic 16, was over-expressed in 3V epithelial cells in the embryo (in scRNA-seq data, Figure 3B-D).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“We confirmed our hypothesis of a common progenitor pool by lineage tracing the progeny of Wnt1+ progenitors (by crossing Wnt1-CRE2 (Lewis et al., 2013) with R26R-Confetti mice (Livet et al., 2007; Snippert et al., 2010), Figure 2H,I.”
- Also stated in: § An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing · plain
“These data support our model of a common progenitor pool that can give rise to both cell types.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing · plain
In the paper
“We also validated the expression of NRP1 protein, an effector of SARS-CoV-2 cell entry and infectivity, in mesenchymal cells (Cantuti-Castelvetri et al., 2020) (Figure 4M).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > ACE2, the SARS-CoV-2 receptor is expressed by mesenchymal cells in the ChP
What the sources say
- Not checked yetcites Cantuti-Castelvetri et al., 2020 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A subset of the Cx3cr1+ macrophages located on the apical ChP surface expressed LYVE1 (Figure 5G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Mesenchymal cell profiles partitioned into fibroblasts and mural cells expressing pericyte and vascular smooth muscle cell (vSMC) markers (Figure 4A, S4A), consistent with cranial mesenchyme and neural crest contributions to the stromal space (Martik and Bronner, 2017; Wilting and Christ, 1989).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
What the sources say
- Not checked yetcites Martik and Bronner, 2017
- Not checked yetcites Wilting and Christ, 1989
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“There were also age-dependent expression of genes encoding secreted proteins (Figure 3H, S3H, Table S3), including the “anti-aging” gene Klotho (Kuro-o et al., 1997; Zhu et al., 2018), which increased with age (Figure 3H).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Analysis of 3V ChP in Wnt1-CRE2::R26R-Confetti mice further revealed Wnt1-lineage contributions to 3V ChP epithelial cells (Figure 2L).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Shisa8, a reprogramming regulator (Schiebinger et al., 2019), was also expressed near the base of acetylated tubulin tufts in multi-ciliated epithelial cells (Figure 2N,O).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
What the sources say
- Not checked yetcites Schiebinger et al., 2019 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SnRNA-seq of embryonic, adult, and aged ChP across all ventricles identified macrophages, neutrophils, dendritic cells, plasma cells, and lymphoid (B- and T-) cells (Figure 5H, S5E,F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“We validated ACE2 protein expression by mesenchymal cells in the stromal space (Figure 4K) and on some epithelial cells in embryonic, adult, and aged ChP (Figure 4K,L, S4K), similar to reports in human ChP (Yang et al., 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > ACE2, the SARS-CoV-2 receptor is expressed by mesenchymal cells in the ChP
What the sources say
- Not checked yetcites Yang et al., 2020
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the embryonic ChP, scRNA-seq profiles spanned eight subsets of immune cells: B cells, lymphocytes, macrophages, basophils, mast cells, dendritic cells, monocytes and neutrophils (Figure 5A,B), each expressing specific cytokine, chemokine, and complement component genes (Figure S5A,B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, epithelial cells in the ChP partitioned into two subpopulations by their weights of topics 6, 11 or 23 (Figure 3B,E, S3F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Our work builds on previous findings (Lun et al., 2015a) to demonstrate the ventricle-specific regionalization of epithelial and mesenchymal cells.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Lun et al., 2015a
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Several interactions were predicted across all ventricles and ages, between immune cells and structural cells (epithelial, mesenchymal and endothelial), in line with the diverse functions assigned to immune cells in other barrier systems (Krausgruber et al., 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
What the sources say
- Not checked yetcites Krausgruber et al., 2020 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Its cognate receptor, IL1R1, was expressed by endothelial, mesenchymal and epithelial cells”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Specifically, non-capillary endothelial cells in the embryonic ChP expressed BBB markers (Cldn5 and Mfsd2a, Topic 11) (Figure 6A), even though the ChP is recognized to lack a classic BBB (Ben-Zvi et al., 2014; Saunders et al., 2018b).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
- Not checked yetcites Ben-Zvi et al., 2014 source
- Not checked yetcites Saunders et al., 2018b
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-1β immunolabeled macrophages in the aged ChP localized to vessel-like structures bridging the ChP with the brain parenchyma (Figure 7F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ventricle-specific identities were maintained in the adult and aged tissue”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The number of significant ligand-receptor interactions between each pair of cell types changed across ventricles and ages (Figure 7A, Figure S7A,B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“uncovered age-dependent changes within ChP cellular signaling networks.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The arterio-venous zonation in the developing embryo was accompanied by enriched capillary marker expression (e.g. Esm1) along the ventricular margin of the ChP, suggesting zonated gene expression in vessels across the developing ChP (Figure 6C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In agreement with recent reports (Van Hove et al., 2019), we found diversity within the BAMs, which segregated into two subsets defined as major histocompatibility complex (MHC) class IIlow and MHC IIhigh.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Van Hove et al., 2019 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 3V and 4V ChP, Bmp5-Bmpr1b LRP expression predicted signaling from mesenchymal to neuro/glial and epithelial cells (Figure 7C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The macrophages expressed markers of border associated macrophages (BAMs) (e.g., Apoe, Ms4a7, Ms4a6c) recently identified in periluminal regions, meninges, and ChP (Van Hove et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Van Hove et al., 2019 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Similarly, we found a subset of macrophages expressing markers previously defined as subdural-specific BAMs (e.g., Lyve1, Ednrb, Colec12; Van Hove et al., 2019) that were enriched in embryonic ChP macrophages in our dataset (Figure S5H).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Van Hove et al., 2019 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, Nov-Notch1 ligand receptor pair (LRP) expression in the 3V ChP and Dlk1-Notch LRP in 4V ChP predicted ventricle-specific signaling from mesenchymal cells to most other cell types (Figure 7C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, Rspo2-Lgr4 LRP expression predicted signaling mainly from neuro/glial cells to epithelial and neuro/glial cells in the LV ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparing single nucleus profiles across ages revealed that arterial, venous, and capillary identities were established across adult ages and ventricles (Figure 6D, S6C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the embryo, topic modeling of scRNA-seq data of vascular cells recovered expression programs associated with capillary (Topic 3), arterial (Topic 8 and 10) and blood-brain barrier (BBB)-associated (Topic 11) cells (Figure 6A, S6A,B, Table S7).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among age-specific interactions, several LRPs were embryonically enriched.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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
“Analysis of cognate ligand-receptor expression patterns across cell types, ventricles and ages (STAR Methods) predicted extensive cellular crosstalk involving all major ChP cell types (Figure 7).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among the ligand-receptor pairs expressed in adult that increased with age, Cxcl12-Ackr3 LRP expression predicted signaling from mesenchymal to endothelial and other cell types (Figure 7D).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“uncovered ventricle- and age-specific gene expression programs for epithelial and mesenchymal cells”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, mesenchymal and epithelial cells had a high number of interactions (Figure 7A, Figure S7B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“additional genes became regionalized in the adult (and persisted into aging)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“its receptor, IL1R1, was enriched in endothelial and mesenchymal cells (Figure 7E).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“described immune cell diversity”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“IL-1β expression was induced in aged ChP macrophages”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Further, in the developing ChP, Efna5-Ephb2 LRP expression predicted signaling from epithelial cells to neuro/glial cells (Figure 7D), suggesting a role for Ephrin signaling in differentiation (similar to the gut; Kania and Klein, 2016).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
What the sources say
- Not checked yetcites Kania and Klein, 2016
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Csf1, a signal for macrophage and monocyte differentiation was expressed by mesenchymal cells and endothelial cells”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IHC revealed enrichment along endothelial structures (Figure 7G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“mapped developing and aging vascular structures”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“We spatially mapped the developing arterio-venous zonation in the embryonic LV ChP in whole explants by combining the pan-endothelial marker PECAM1 with markers for arteries (Acta2+, Vwf+) and veins (Acta2−, Vwf+) (Vanlandewijck et al., 2018).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
- Not checked yetcites Vanlandewijck et al., 2018 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we characterized ChP cell types across ventricles and ages”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Most ChP macrophages shared signature genes recently described for adult ChP macrophages (Jordão et al., 2019a)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Jordão et al., 2019a
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Overall, we observed an upregulation of the inflammatory signals in the aged ChP in agreement with prior studies (Baruch et al., 2014) that was reflected in expression of Ifit1 and Il1b in aged epithelial cells.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Baruch et al., 2014 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed that some, but not all, epiplexus cells expressed LYVE1”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, in the analysis of epithelial cells, one topic was enriched for immediate early genes (Topic 19, Figure S3B,C)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“and were Sall1 negative (Hammond et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Hammond et al., 2019 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“because it was reduced in single nucleus profiles (Lacar et al., 2016) (Figure S3D).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
- Not checked yetcites Lacar et al., 2016 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In summary, our study provides a comprehensive map of the molecular, cellular and spatial diversity of each ChP of the developing, adult, and aging mouse brain.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“genes upregulated during development, such as Cd206/Mrc1, were downregulated in adult and aged macrophages.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While we did not uncover a transcriptional signature purely for epiplexus cells”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“because of strong batch effects between replicates.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, mesenchymal cells were the cell type with the most predicted interactions with other ChP cell types.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting a common progenitor pool for both epithelial and neuronal cells may exist in the ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“For example, Ins2 was expressed in the 3V ChP, supporting the model that the ChP is an internal source of insulin for the brain (Mazucanti et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
- Not checked yetcites Mazucanti et al., 2019 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, epithelial cells likely adapt to fulfill age-dependent functions in the brain.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these interactions may contribute to age-dependent macrophage migration and infiltration of the ChP brain immune barrier.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that myeloid cell signaling maturation for Csf1r expressing cells exists in the ChP throughout life (Figure S7C, Table S7).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Enhanced putative IL-1β signaling between macrophages, endothelial and mesenchymal cells in aging
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Overall, these results identify molecular identities and vascular organization of ChPs across ventricles and ages that match vascular patterning in the human ChP (Hudson, 1960).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
- Not checked yetcites Hudson, 1960 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Gene programs and graded expression patterns, particularly across 4V ChP epithelial cells, may arise from the segmental development of the 4V ChP from distinct rhombomeres (Awatramani et al., 2003; Hunter and Dymecki, 2007).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Awatramani et al., 2003 source
- Not checked yetcites Hunter and Dymecki, 2007
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating heterogeneity in immune cells positioned on the ChP surface.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“These maturation dependent changes agree with a recent report of BAMs (Van Hove et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Van Hove et al., 2019 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our data further clarify that this diversity is likely maturation-dependent”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We endeavored to isolate pure ChP by dissecting along anatomically defined tissue boundaries, which were at times limited (e.g., 3V ChP that has less defined borders).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION > Limitations of the study
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the previously described diversity reflect instead a transition state between embryo and adult.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 48
- Probably not a substantial claim. 22
- The quote only partly states this claim. 2
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 tissue maturation was accompanied by a distinct shift in gene expression between embryo and adult/aged ChP (Figure 1F-H, S1F,G), canonical cell-type markers were conserved across ages and ventricles (Figure 1I, Figure S1H,I).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Molecular survey defines the cellular composition of the ChP across ventricles and ages
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
“The diversity of embryonic glia and neuronal populations observed in scRNA-seq was confirmed by snRNA-seq and expanded to adult and aged ChP (Figure S2D,E) (Dulken et al., 2017; Mizrak et al., 2019; Shah et al., 2018).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
What the sources say
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
“Notably, actively cycling cell subsets were present within each of the six major cell classes in the developing ChP (Figure S1D) and were enriched along the base of the ChP proximal to the brain (Figure S1E).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Molecular survey defines the cellular composition of the ChP across ventricles and ages
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The predicted progenitors expressed proliferation (Mki67) and known markers (Pax6, Rspo2/3, Wnt5a/3a/1, Fabp7, clusters 7 and 8 in Figure 2A,B S2B; STAR Methods), previously reported for precursors of ependymal cells and cortical neurons (Kriegstein and Alvarez-Buylla, 2009), with Wnt1 having the most specific expression (Figure S2G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
What the sources say
- Not checked yetcites Kriegstein and Alvarez-Buylla, 2009 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“We captured neuronal (Tubb3 expressing) and glia-like (Slc1a3/EAAT1 or GFAP expressing) cells in the ChP across all ages, validated by immunostaining (Figures 1C,D,I, S1J-L), in agreement with previous studies (Lindvall et al., 1978).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
What the sources say
- Not checked yetcites Lindvall et al., 1978 source
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
“Subsets of neurons expressed markers of intermediate progenitors (e.g. Eomes/Tbr2) or of immature neurons (e.g. Neurod1/2, Dlx1/2), and various neuropeptides (e.g. Vgf, Chgb) (Figure S2B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Neuronal and glial cell populations in the ChP
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SnRNA-seq of embryonic, adult, and aged ChP identified the same major cell classes in each ventricle (as in scRNA-seq of embryonic samples, Figure 1F), with conservation of overall cellular composition with age.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Molecular survey defines the cellular composition of the ChP across ventricles and ages
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
“Comparing patterns across three age groups profiled by snRNA-seq, we found both age-invariant and age-dependent expression patterns, including regionalized patterns, with the main shift occurring from embryo to adult and then persisting into aging (Figure 3F,G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
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
“Several topics reflected cross-ventricle regionalized gene programs (Topics 3, 6, 11, 14, 16, and 23), having differential weights between cells from different ventricles (Figure 3B, S3C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“Among age-dependent ventricle-invariant genes, embryonic fibroblasts expressed higher levels of developmental and morphogenesis genes, whereas the adult and aged fibroblasts upregulated transporters, receptors, peptidase and proteolytic activity genes (Figure 4I, S4H,I).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
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In the paper
“Notably, the proportion of replicating epithelial cells was reduced from ~10% in embryonic ChP to ~1% in adult ChP, with an overall shift towards more mature cells compared to ciliogenic epithelial cells (p-value < 0.05, t-test on fraction of cells, Figure S2L).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
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In the paper
“Wnt1-derived epithelial cells in the maturing 4V ChP extended away from the URL, and Wnt1-derived neurons were in close proximity to progenitors in the URL (Figure 2J,K).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
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In the paper
“In fibroblasts, we found both age-invariant and age-dependent patterns, including regionalized patterns (Figure 4G,H, Table S5).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
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In the paper
“These were enriched for specialized programs across ages: Embryonic epithelia upregulated genes for developmental processes (Figure 3K, S3K), while aged epithelia upregulated host-defense programs (Figure 3L, FDR q-value < 0.01, GOrilla (Eden et al., 2007, 2009;Baruch et al., 2014).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
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In the paper
“For example, in adult ChP Slc12a2 (NKCC1), Kcnj13 (Kir7.1), and Slc4a5 (NBC4) were upregulated (see also (Xu et al., 2021)), while Aqp1 was modestly downregulated (Figure 3H, S3G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
What the sources say
- Not checked yetcites Xu et al., 2021
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In the paper
“We mapped the differentiating populations to distinct spatial boundaries within each ventricle (Figure 2P-R), with progenitor cells located near the ChP-brain boundary (by smFISH of Rspo1/2/3; Wnt2b/3a/5a; Axin2) (Figure S2H-K).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > An inferred common progenitor pool for epithelial and neural cells validated by lineage tracing
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In the paper
“As in epithelial cells, age-dependent fibroblast genes typically changed postnatally and were maintained in aged ChP (Figure 4H).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Mesenchymal cell programs are regionalized across brain ventricles
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In the paper
“Macrophages were the most prevalent and were associated with blood vessels across all ages (Figure S5G; Shipley et al., 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Shipley et al., 2020 source
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In the paper
“In the embryo, epithelial cells formed the largest cell class in each ChP (by scRNA-seq, Figure S1B) and partitioned into subsets representing cycling, newly differentiated cells undergoing ciliogenesis (above, Figure 2N), and mature cells (Figure 3A).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Epithelial cell programs are regionalized across brain ventricles in all ages
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In the paper
“Cx3cr1-GFP-expressing cells tiled across the ChP (Figure 5E; Cui et al., 2020), with the subset expressing SLC40A1 located proximal to major vessels, suggesting roles in regulating iron homeostasis (Figure 5F).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Cui et al., 2020 source
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In the paper
“However, in contrast to Van Hove et al., our data revealed that this separation was age-dependent and potentially represented a maturation-dependent shift from MHC IIlow to MHC IIhigh (Figure 5I, S5I,J, Table S6).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
What the sources say
- Not checked yetcites Van Hove et al., 2019 source
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In the paper
“The stereotyped vascular organization was retained in aged ChP (Figure 6F), where Vwf and Selp (P-selectin) expression were also detected (Figure 6G).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
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In the paper
“Notably, topic modeling of embryonic ChP cells also uncovered a previously unknown brain barrier transition zone embedded in the molecular and vascular map of the ChP, which we validated across ages.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
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In the paper
“For example, mesenchymal cells (fibroblasts and pericytes) expressed Pdgfra and Pdgfrb respectively, and epithelial and endothelial cells expressed their cognate ligands, Pdgfa and Pdgfb respectively (Figure S7C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“In adult and aged LV ChP, IHC showed that arteries and veins were regularly segmented across the tissue (Figure 6E,F; Shipley et al., 2020) and connected by an expanded capillary-like network (Figure S6D) similar to human tissue (Hudson, 1960).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
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In the paper
“For example, CD206 (Mrc1, mannose receptor C-type I) expressed by embryonic macrophages was downregulated in adults, whereas CD74 (MHC class II associated protein) was upregulated in adult and aged macrophages vs. embryos (Figure 5J-L, Figure S5H).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Homeostatic macrophage diversity within ChP across ages
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In the paper
“Comparing significant interactions across ventricles or ages revealed age- or ventricle-dependent interactions and overall differences in the number of interactions (Figure 7B-D).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“Cldn5 expression persisted in a subset of endothelial cells in snRNA-seq from all ages (Figure 6I, S6C), and CLDN5 protein was prominent in the major arteries bifurcating from the choroidal artery and extending into the ChP (Figure 6J, K, S6I).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
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In the paper
“IHC revealed VWF and SELP colocalized to enlarged luminal domains of vessels in aged mice (Figure 6H), suggesting age-associated vascular damage.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
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In the paper
“The majority of significantly interacting cell type pairs involved mesenchymal cells (FDR<0.05, 60%, 70% and 85% in embryonic, adult and aged, respectively), followed by epithelial cells (FDR<0.05, 45%, 55% and 42% in embryonic, adult and aged, respectively).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“either by activation of expression (for genes not expressed in the embryo) or by restriction of expression (for genes expressed across ventricles in the embryo).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
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In the paper
“Other notable interactions included Vegfa in epithelial and mesenchymal cells and its receptor Flt1 on endothelial cells (Figure S7C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“Histological analyses revealed arteries developing obliquely across the ChP and veins running along the ventricular free margin of the tissue (Figure 6B).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
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In the paper
“Notably, in a more conservative, degree-preserving permutation test, the number of predicted interactions between most cell type pairs was not statistically significant (Figure S7D), indicating the dominance of a cell type in the crosstalk across all cells and not specific pairs.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“We found significant individual interactions between each pair of cell types across all ventricles and ages, with specific cell type pairs having a significant enrichment in the number of interactions (Figure 7A, S7A,B, Table S8).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“While we did not observe overt regionalization of endothelial cell programs, venous markers were enriched in the 3V ChP across all ages (Figure 6D, S6F,G), likely resulting from capture of the proximal vein of Galen (Mancini et al., 2015) (Figure S6H).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
- Not checked yetcites Mancini et al., 2015 source
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In the paper
“Moreover, Plvap, which marks diaphragms of fenestrated endothelial cells (Herrnberger et al., 2012), scored highly in Topic 3 from scRNA-seq of embryonic cells (Figure 6A), and was also identified in adult and aged snRNA-seq profiles (Figure S6C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Arterio-venous zonation and blood brain barrier protein expression in ChP vasculature
What the sources say
- Not checked yetcites Herrnberger et al., 2012 source
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In the paper
“Wnt5a, a regulator of 4V ChP and hindbrain development (Kaiser et al., 2019), was most robustly expressed by mesenchymal cells and its receptor Ror1 was expressed, amongst others, by epithelial cells, suggesting lifelong contributions to ChP function (Figure S7C).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
What the sources say
- Not checked yetcites Kaiser et al., 2019 source
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In the paper
“Essentially all major ChP cell types, and in particular ChP fibroblasts, also expressed many secreted factors found in CSF, including Igf2 (Lehtinen et al., 2011).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Lehtinen et al., 2011 source
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In the paper
“adult macrophages upregulated CD74, a chaperone of antigen presentation protein that was even further upregulated in the aged ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
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In the paper
“the epithelial cell clusters scoring highly for IEG genes (Figure S2D)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
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In the paper
“because they had very high expression of mitochondrial genes.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
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In the paper
“Our profiles of ChP immune cell populations revealed spatial organization and age-dependent expression across ventricles and within the ChP.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
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In the paper
“The out-of-bag error was 1.7%.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
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In the paper
“The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier.”
- Also stated in: § INTRODUCTION · boosted
“The choroid plexus (ChP) is an essential brain barrier known primarily as a source of cerebrospinal fluid (CSF) and comprises an analogous set of four tissue structures located in each brain ventricle.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > Abstract
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- Also stated in: § INTRODUCTION · boosted
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In the paper
“Bulk profiling of whole tissue (Liddelow et al., 2010; Lun et al., 2015b; Silva-Vargas et al., 2016) or sorted subpopulations (Lun et al., 2015b) indicates that each ChP retains a developmental blueprint of its origins along the body axis, with ventricle-specific transcriptomes and secretomes for the lateral and 4th ventricle ChPs (Lun et al., 2015a).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > INTRODUCTION
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In the paper
“The foundation of the ChP is an epithelial sheet that, together with a network of vasculature and diverse cell types, regulates CSF secretion and governs its composition by de novo protein synthesis and selective transcytosis of blood-borne factors (Damkier et al., 2013; Ghersi-Egea et al., 2018; Lun et al., 2015a; Saunders et al., 2018b).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > INTRODUCTION
What the sources say
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In the paper
“Each ChP develops independently from distinct locations along the roofplate, where capillaries, mesenchymal and neural crest cells invaginate the neuroepithelium (Hunter and Dymecki, 2007; Lun et al., 2015a; Wilting and Christ, 1989).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > INTRODUCTION
What the sources say
- Not checked yetcites Hunter and Dymecki, 2007
- Not checked yetcites Lun et al., 2015a
- Not checked yetcites Wilting and Christ, 1989
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In the paper
“These data highlight the potential of mesenchymal and epithelial ChP cells to facilitate viral particle entry into the CSF (Pellegrini et al., 2020b, 2020a; Wu et al., 2020) in all ventricles and ages and to contribute to neurological sequelae associated with SARS-CoV-2 infection (Ellul et al., 2020).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > ACE2, the SARS-CoV-2 receptor is expressed by mesenchymal cells in the ChP
What the sources say
- Not checked yetcites Pellegrini et al., 2020b
- Not checked yetcites Pellegrini et al., 2020a
- Not checked yetcites Wu et al., 2020
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In the paper
“In addition, there were some differences between predicted significant interactions from scRNA-seq vs. snRNA-seq for embryo ChP, which may reflect differences in cell type recovery between methods (Figure S7A).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > RESULTS > Ligand-receptor analysis identifies mesenchymal cells as an interaction hub across ages and ventricles
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In the paper
“Multiple comparisons ANOVA was employed using statistical software package Graphpad PRISM. Data are represented as mean ± SEM. P < 0.05 was considered significant.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
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In the paper
“We cannot rule out the possibility that we may miss some lower expressed genes of interest to ChP biology due to the limitations in depth of coverage.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION > Limitations of the study
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In the paper
“we excluded nuclei that had more than 10% of total UMI’s mapped to mitochondrial genes.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
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In the paper
“As CellPhoneDB is developed for human ligand-cognate receptor pairs”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
- Not checked yetcites Efremova et al., 2020 source
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In the paper
“cellular health was particularly challenging for adult and aged tissues, ultimately leading us to favor differential sample processing”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION > Limitations of the study
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In the paper
“and may reflect a response to tissue dissociation (van den Brink et al., 2017)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
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In the paper
“The ChP is considered to be a primary producer of CSF and CSF-distributed factors (Ghersi-Egea et al., 2018; Lun et al., 2015a; Saunders et al., 2018b)”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION
What the sources say
- Not checked yetcites Ghersi-Egea et al., 2018 source
- Not checked yetcites Lun et al., 2015a
- Not checked yetcites Saunders et al., 2018b
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In the paper
“All mouse work was performed in accordance with the Institutional Animal Care and Use Committees (IACUC) and relevant guidelines of Boston Children’s Hospital and Masaryk University.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Doublets were clearly identifiable as forming their own clusters with dual expression of marker genes of distinct subsets (e.g., epithelial genes and endothelial genes) and were removed from further analysis and any visualizations.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Batch correction was performed for each cell type separately using ComBat as implemented in the R package sva (Leek et al., 2012), using the default parametric adjustment mode.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
- Not checked yetcites Leek et al., 2012 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of four independent explants were quantified.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
In the paper
“Nucleus doublets were identified using the R package DoubletFinder (version DoubletFinder_2.0.2, (McGinnis et al., 2019).”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
- Not checked yetcites McGinnis et al., 2019 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“This strategy subsequently introduced additional computational challenges in comparison of the two datasets.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION > Limitations of the study
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“To address ambient (background) RNA and other confounders we applied CellBender (Fleming et al., 2019) to each sample separately”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
What the sources say
- Not checked yetcites Fleming et al., 2019
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“we fit a range of K and tolerance values and picked values that gave us robust topics and where we mostly saturated the number of informative topics found.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > STAR METHODS > METHOD DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“required adjustments to our computational tools including the use of topic modeling.”
§ A cellular and spatial map of the choroid plexus across brain ventricles and ages > DISCUSSION > Limitations of the study
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The third ventricle is the least explored of the choroid plexuses.
“The less-accessible third ventricle is the least explored, and boundaries of all ChPs with adjacent neural tissues remain poorly defined.”
The paper relies on this without support.
The boundaries of all choroid plexuses with adjacent neural tissues remain poorly defined.
“The less-accessible third ventricle is the least explored, and boundaries of all ChPs with adjacent neural tissues remain poorly defined.”
The paper relies on this without support.
Earlier efforts to address deficiencies in choroid plexus knowledge were limited by the lack of techniques to access, isolate, and comprehensively profile the ChP across brain ventricles and ages.
“Earlier efforts to address these deficiencies were limited by the lack of techniques to access, isolate, and comprehensively profile the ChP across brain ventricles and ages.”
The paper relies on this without support.
The lack of a detailed cellular and molecular map for the choroid plexus has been a major obstacle to elucidating its roles in instructing brain development, brain function, understanding its barrier properties, and unlocking its lifelong therapeutic potential.
“The lack of a detailed cellular and molecular map for the ChP has been a major obstacle to elucidating its roles in instructing brain development, brain function, understanding its barrier properties, and unlocking its lifelong therapeutic potential.”
The paper relies on this without support.
The choroid plexus-cerebrospinal fluid system is implicated in a growing number of neurologic conditions.
“Since the ChP-CSF system is implicated in a growing number of neurologic conditions”
The paper relies on this without support.
Transitions between cell states and ages are continuous.
“Transitions between cell states and ages are continuous”
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?
In the citing paper
“but to our knowledge no snRNA-seq study exists on the human choroid plexus, in health or disease22.”
From Dysregulation of brain and choroid plexus cell types in severe COVID-19 (2021) · cites this paper as [22]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rspo3 probe is labeled as Rspo1
MinorThe probe listed for Rspo3 is labeled "mm-Rspo1," even though a separate Rspo1 probe is listed with a different reference number. The Rspo3 probe identity is therefore inconsistent within the probe list.
“Rspo3 (mm-Rspo1, Ref: 402011-C3)”
“Rspo1 (mm-Rspo1, Ref: 401991)”
Citations
Cites
Inference of Population Structure Using Multilocus Genotype Data
Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871
(2008) · Journal of Machine Learning Research · Cited by 33,051
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Community structure in social and biological networks
Girvan, M., & Newman, M. E. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122653799 · Cited by 15,502
Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Blei, D. M., Ng, A. Y., & Jordan, M. I. (2002) · The MIT Press eBooks · doi:10.7551/mitpress/1120.003.0082 · Cited by 12,677
UMAP: Uniform Manifold Approximation and Projection for Dimension Reduction
McInnes, L., Healy, J., & Melville, J. (2018) · arXiv · doi:10.48550/arxiv.1802.03426 · Cited by 7,101
Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E., & Storey, J. D. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts034 · Cited by 6,231
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572
Dimensionality reduction for visualizing single-cell data using UMAP
Becht, E., McInnes, L., Healy, J., Dutertre, C.-A., Kwok, I. W. H., Ng, L. G., Ginhoux, F., & Newell, E. W. (2019) · Nature Biotechnology · doi:10.1038/nbt.4314 · Cited by 5,358
Flagged first, then by citations
2 of the 136 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Fleming, 2019, CellBender remove-background: A deep generative model for unsupervised removal of background noise from scRNA-seq datasets, BioRxiv, 791699
Cited by
Sorted by citations
Fleming, S. J., Chaffin, M. D., Arduini, A., Akkad, A.-D., Banks, E., Marioni, J. C., Philippakis, A. A., Ellinor, P. T., & Babadi, M. (2023) · Nature Methods · doi:10.1038/s41592-023-01943-7 · Cited by 867
Dysregulation of brain and choroid plexus cell types in severe COVID-19
Yang, A. C., Kern, F., Losada, P. M., Agam, M. R., Maat, C. A., Schmartz, G. P., Fehlmann, T., Stein, J. A., Schaum, N., Lee, D. P., et al. (2021) · Nature · doi:10.1038/s41586-021-03710-0 · Cited by 620
Human CNS barrier-forming organoids with cerebrospinal fluid production
Pellegrini, L., Bonfio, C., Chadwick, J., Begum, F., Skehel, M. J., & Lancaster, M. A. (2020) · Science · doi:10.1126/science.aaz5626 · Cited by 469
Transforming the understanding of brain immunity
Castellani, G., Croese, T., Peralta Ramos, J. M., & Schwartz, M. (2023) · Science · doi:10.1126/science.abo7649 · Cited by 386
Aburto, M. R., & Cryan, J. F. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00890-0 · Cited by 407
Metadata
- Authors
- Dani, N., Herbst, R. H., McCabe, C., Green, G. S., Kaiser, K., Head, J. P., Cui, J., Shipley, F. B., Jang, A., Dionne, D., Nguyen, L., Rodman, C., Riesenfeld, S. J., Prochazka, J., Prochazkova, M., Sedlacek, R., Zhang, F., Bryja, V., Rozenblatt-Rosen, O., Habib, N., Regev, A., & Lehtinen, M. K.
- Affiliations
- Boston Children's Hospital (US)
- Broad Institute (US)
- Hebrew University of Jerusalem (IL)
- Masaryk University (CZ)
- Corresponding author
- Habib, Naomi
- Regev, Aviv
- Lehtinen, Maria K.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 184
- Issue
- 11
- Pages
- 3056-3074.e21
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8214809
- OpenAlex
- W3157400350
- Semantic Scholar
- 2401a5c95b12f729e979e5eaaabc8c3df3e80d3b
- Cited by
- 388
- References
- 136
- Citations by year
- 2026: 71 · 2025: 97 · 2024: 79 · 2023: 64 · 2022: 41 · 2021: 22
- FWCI
- 16.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 391 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Grantová Agentura České Republiky (LM2018129, GX19-28347X)
- Israel Science Foundation (1709/19)
- New York Stem Cell Foundation
- HHMI
- National Science Foundation
- Helen Hay Whitney Foundation
- NSF
- Broad Institute
- NIH (1U54HD090255, T32 HL110852)
- AFAR
- Ministerstvo Školství, Mládeže a Tělovýchovy (RVO 68378050)
- European Regional Development Fund
- Akademie Věd České Republiky (LM2018126l CZ.1.05/2.1.00/19.0395, CZ.02.1.01/0.0/0.0/16_013/0001789)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- choroid plexus, cerebrospinal fluid, blood-CSF barrier, brain ventricles, single-cell atlas, spatial atlas, mouse brain development, brain aging, choroid plexus epithelial cells, progenitor cells, lineage tracing, fibroblasts, macrophages, interleukin-1β signaling, host defense genes
- MeSH terms
- Age Factors, Aging, Animals, Blood-Brain Barrier, Brain, Brain Diseases, Cell Differentiation, Choroid Plexus, Epithelial Cells, Female, Male, Mice, Inbred C57BL, Signal Transduction, Cell Lineage, Mice, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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