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A cellular and spatial map of the choroid plexus across brain ventricles and ages
Open accessPublished version of a preprint
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
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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
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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
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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
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- It may state two separate claims as one. 48
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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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
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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
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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
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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
“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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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
“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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In 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
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.
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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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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
“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
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
“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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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 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
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
“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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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 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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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
“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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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
“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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
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
“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
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
“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
Load-bearingStrength:hedged· 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
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“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
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
“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
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
“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
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:plain· not yet calibratedSingle caseTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The 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
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.
None of the sources cited for this claim have been checked yet.
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
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Also stated in: § INTRODUCTION · boosted
None of the sources cited for this claim have been checked yet.
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
What the sources say
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 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
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.
None of the sources cited for this claim have been checked yet.
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
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.
None of the sources cited for this claim have been checked yet.
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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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 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
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 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
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.
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
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
“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
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
“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
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
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
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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
(2003) · Journal of Machine Learning Research · doi:10.5555/944919.944937 · Cited by 32,337
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
McGinnis, C. S., Murrow, L. M., & Gartner, Z. J. (2019) · Cell Systems · doi:10.1016/j.cels.2019.03.003 · Cited by 4,521
La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M. E., Lönnerberg, P., Furlan, A., et al. (2018) · Nature · doi:10.1038/s41586-018-0414-6 · Cited by 4,118
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Schmitz, J., Owyang, A. M., Oldham, E. R., Song, Y., Murphy, E., McClanahan, T. K., Zurawski, G., Moshrefi, M., Qin, J., Li, X., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.09.015 · Cited by 3,773
Efremova, M., Vento-Tormo, M., Teichmann, S. A., & Vento-Tormo, R. (2020) · Nature Protocols · doi:10.1038/s41596-020-0292-x · Cited by 3,449
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
Finak, G., McDavid, A., Yajima, M., Deng, J., Gersuk, V., Shalek, A. K., Slichter, C. K., Miller, H. W., McElrath, M. J., Prlic, M., et al. (2015) · Genome Biology · doi:10.1186/s13059-015-0844-5 · Cited by 3,159
(2012) · doi:10.1016/j.jmoldx.2011.08.002 · Cited by 2,567
The Glial Nature of Embryonic and Adult Neural Stem Cells
Kriegstein, A., & Alvarez-Buylla, A. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135600 · Cited by 2,475
Hammond, T. R., Dufort, C., Dissing-Olesen, L., Giera, S., Young, A., Wysoker, A., Walker, A. J., Segel, M., Nemesh, J., Saunders, A., et al. (2018) · doi:10.1101/406140 · Cited by 2,225
Neurological associations of COVID-19
Ellul, M. A., Benjamin, L., Singh, B., Lant, S., Michael, B. D., Easton, A., Kneen, R., Defres, S., Sejvar, J., & Solomon, T. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30221-0 · Cited by 2,156
Nervous system involvement after infection with COVID-19 and other coronaviruses
Wu, Y., Xu, X., Chen, Z., Duan, J., Hashimoto, K., Yang, L., Liu, C., & Yang, C. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.03.031 · Cited by 2,046
Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N., Klein, A. M., van Rheenen, J., Simons, B. D., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.016 · Cited by 1,951
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
Cantuti-Castelvetri, L., Ojha, R., Pedro, L. D., Djannatian, M., Franz, J., Kuivanen, S., van der Meer, F., Kallio, K., Kaya, T., Anastasina, M., et al. (2020) · Science · doi:10.1126/science.abd2985 · Cited by 1,925
A molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 1,892
Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system
Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., Sanes, J. R., & Lichtman, J. W. (2007) · Nature · doi:10.1038/nature06293 · Cited by 1,876
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
Diffusion pseudotime robustly reconstructs lineage branching
Haghverdi, L., Büttner, M., Wolf, F. A., Buettner, F., & Theis, F. J. (2016) · Nature Methods · doi:10.1038/nmeth.3971 · Cited by 1,385
Extracellular matrix: A dynamic microenvironment for stem cell niche
Gattazzo, F., Urciuolo, A., & Bonaldo, P. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.01.010 · Cited by 1,362
The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis
Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., & Andrews, N. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.01.003 · Cited by 1,275
Reboldi, A., Coisne, C., Baumjohann, D., Benvenuto, F., Bottinelli, D., Lira, S., Uccelli, A., Lanzavecchia, A., Engelhardt, B., & Sallusto, F. (2009) · Nature Immunology · doi:10.1038/ni.1716 · Cited by 1,206
A revised airway epithelial hierarchy includes CFTR-expressing ionocytes
Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., et al. (2018) · Nature · doi:10.1038/s41586-018-0393-7 · Cited by 1,206
Self-citationLi, Q., Cheng, Z., Zhou, L., Darmanis, S., Neff, N. F., Okamoto, J., Gulati, G., Bennett, M. L., Sun, L. O., Clarke, L. E., et al. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.006 · Cited by 1,129
Van Hove, H., Martens, L., Scheyltjens, I., De Vlaminck, K., Pombo Antunes, A. R., De Prijck, S., Vandamme, N., De Schepper, S., Van Isterdael, G., Scott, C. L., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0393-4 · Cited by 1,074
Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations
van den Brink, S. C., Sage, F., Vértesy, Á., Spanjaard, B., Peterson-Maduro, J., Baron, C. S., Robin, C., & van Oudenaarden, A. (2017) · Nature Methods · doi:10.1038/nmeth.4437 · Cited by 1,072
Massively parallel single-nucleus RNA-seq with DroNc-seq
Habib, N., Avraham-Davidi, I., Basu, A., Burks, T., Shekhar, K., Hofree, M., Choudhury, S. R., Aguet, F., Gelfand, E., Ardlie, K., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4407 · Cited by 1,069
Self-citationMfsd2a is critical for the formation and function of the blood-brain barrier
Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., & Gu, C. (2014) · Nature · doi:10.1038/nature13324 · Cited by 1,037
Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation
Jordão, M. J. C., Sankowski, R., Brendecke, S. M., Sagar, Locatelli, G., Tai, Y.-H., Tay, T. L., Schramm, E., Armbruster, S., Hagemeyer, N., et al. (2019) · Science · doi:10.1126/science.aat7554 · Cited by 843
Schiebinger, G., Shu, J., Tabaka, M., Cleary, B., Subramanian, V., Solomon, A., Gould, J., Liu, S., Lin, S., Berube, P., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.006 · Cited by 829
Self-citationNew Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain
Sawamoto, K., Wichterle, H., González-Pérez, Ó., Cholfin, J. A., Yamada, M., Spassky, N., Murcia, N. S., García‐Verdugo, J. M., Marín, Ó., Rubenstein, J. L. R., et al. (2006) · Science · doi:10.1126/science.1119133 · Cited by 803
Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein
Chuang, P., & McMahon, A. P. (1999) · Nature · doi:10.1038/17611 · Cited by 798
Forebrain gene expression domains and the evolving prosomeric model
Puelles, L., & Rubenstein, J. L. R. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00234-0 · Cited by 734
Development and functions of the choroid plexus–cerebrospinal fluid system
Lun, M. P., Monuki, E. S., & Lehtinen, M. K. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3921 · Cited by 719
Self-citationDiscovering motifs in ranked lists of DNA sequences
Eden, E., Lipson, D., Yogev, S., & Yakhini, Z. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030039 · Cited by 696
Shechter, R., Miller, O., Yovel, G., Rosenzweig, N., London, A., Ruckh, J., Kim, K.-W., Klein, E., Kalchenko, V., Bendel, P., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.02.012 · Cited by 683
Diffusion maps for high-dimensional single-cell analysis of differentiation data
Haghverdi, L., Buettner, F., & Theis, F. J. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv325 · Cited by 649
The cerebrospinal fluid provides a proliferative niche for neural progenitor cells
Lehtinen, M. K., Zappaterra, M. W., Chen, X., Yang, Y. J., Hill, A. D., Lun, M., Maynard, T., Gonzalez, D., Kim, S., Ye, P., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.023 · Cited by 648
Self-citationMechanisms of ephrin–Eph signalling in development, physiology and disease
Kania, A., & Klein, R. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.16 · Cited by 645
destiny : diffusion maps for large-scale single-cell data in R
Angerer, P., Haghverdi, L., Büttner, M., Theis, F. J., Marr, C., & Buettner, F. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btv715 · Cited by 640
A High-Resolution Anatomical Atlas of the Transcriptome in the Mouse Embryo
Diez-Roux, G., Banfi, S., Sultan, M., Geffers, L., Anand, S., Rozado, D., Magen, A., Canidio, E., Pagani, M., Peluso, I., et al. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000582 · Cited by 638
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function
Kleinridders, A., Ferris, H. A., Cai, W., & Kahn, C. R. (2014) · Diabetes · doi:10.2337/db14-0568 · Cited by 625
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
Aging-induced type I interferon response at the choroid plexus negatively affects brain function
Baruch, K., Deczkowska, A., David, E., Castellano, J. M., Miller, O., Kertser, A., Berkutzki, T., Barnett-Itzhaki, Z., Bezalel, D., Wyss-Coray, T., et al. (2014) · Science · doi:10.1126/science.1252945 · Cited by 615
Cerebrospinal fluid secretion by the choroid plexus
Damkier, H. H., Brown, P. D., & Praetorius, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00004.2013 · Cited by 606
Pellegrini, L., Albecka, A., Mallery, D. L., Kellner, M. J., Paul, D., Carter, A. P., James, L. C., & Lancaster, M. A. (2020) · Cell stem cell · doi:10.1016/j.stem.2020.10.001 · Cited by 562
GenePaint.org: an atlas of gene expression patterns in the mouse embryo
Visel, A. (2004) · Nucleic Acids Research · doi:10.1093/nar/gkh029 · Cited by 528
Role for Spi-C in the development of red pulp macrophages and splenic iron homeostasis
Kohyama, M., Ise, W., Edelson, B. T., Wilker, P. R., Hildner, K., Mejia, C., Frazier, W. A., Murphy, T. L., & Murphy, K. M. (2009) · Nature · doi:10.1038/nature07472 · Cited by 479
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
Ghersi-Egea, J.-F., Strazielle, N., Catala, M., Silva-Vargas, V., Doetsch, F., & Engelhardt, B. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1807-1 · Cited by 436
Structural cells are key regulators of organ-specific immune responses
Krausgruber, T., Fortelny, N., Fife-Gernedl, V., Senekowitsch, M., Schuster, L. C., Lercher, A., Nemc, A., Schmidl, C., Rendeiro, A. F., Bergthaler, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2424-4 · Cited by 434
Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages
Haldar, M., Kohyama, M., So, A. Y.-L., KC, W., Wu, X., Briseño, C. G., Satpathy, A. T., Kretzer, N. M., Arase, H., Rajasekaran, N. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.01.069 · Cited by 431
A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells
Singer, M., Wang, C., Cong, L., Marjanovic, N. D., Kowalczyk, M. S., Zhang, H., Nyman, J., Sakuishi, K., Kurtuluş, S., Gennert, D. G., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.052 · Cited by 422
Self-citationLung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting
Cohen, M., Giladi, A., Gorki, A.-D., Gelbard-Solodkin, D., Zada, M., Hladik, A., Miklosi, A., Salame, T., Halpern, K. B., David, E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.009 · Cited by 418
Karimy, J. K., Zhang, J., Kurland, D. B., Theriault, B. C., Durán, D., Stokum, J. A., Furey, C. G., Zhou, X., Mansuri, M. S., Montejo, J. D., et al. (2017) · Nature Medicine · doi:10.1038/nm.4361 · Cited by 410
Nuclear RNA-seq of single neurons reveals molecular signatures of activation
Lacar, B., Linker, S. B., Jaeger, B. N., Krishnaswami, S. R., Barron, J. J., Kelder, M. J. E., Parylak, S. L., Paquola, A. C. M., Venepally, P., Novotny, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11022 · Cited by 405
Lim, H. Y., Lim, S. Y., Tan, C. K., Thiam, C. H., Goh, C. C., Carbajo, D., Chew, S. H. S., See, P., Chakarov, S., Wang, X. N., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.06.008 · Cited by 384
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349
Shen, M. D., Nordahl, C. W., Young, G. S., Wootton-Gorges, S. L., Lee, A., Liston, S. E., Harrington, K. R., Ozonoff, S., & Amaral, D. G. (2013) · Brain · doi:10.1093/brain/awt166 · Cited by 345
Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma
Grapp, M., Wrede, A., Schweizer, M., Hüwel, S., Galla, H., Snaidero, N., Simons, M., Bückers, J., Low, P. S., Urlaub, H., et al. (2013) · Nature Communications · doi:10.1038/ncomms3123 · Cited by 338
Dulken, B. W., Leeman, D. S., Boutet, S. C., Hebestreit, K., & Brunet, A. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.060 · Cited by 334
van Houten, M., Posner, B. I., Kopriwa, B. M., & Brawer, J. R. (1979) · Endocrinology · doi:10.1210/endo-105-3-666 · Cited by 321
Brooks, E., & Wallingford, J. B. (2014) · Current Biology · doi:10.1016/j.cub.2014.08.047 · Cited by 320
Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells
Silva-Vargas, V., Maldonado-Soto, A. R., Mizrak, D., Codega, P., & Doetsch, F. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.06.013 · Cited by 306
Lewis, A. E., Vasudevan, H. N., O’Neill, A. K., Soriano, P., & Bush, J. O. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.04.026 · Cited by 289
Blood–brain-barriers in aging and in Alzheimer’s disease
Marques, F., Sousa, J. C., Sousa, N., & Palha, J. A. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-38 · Cited by 285
Cilia-based flow network in the brain ventricles
Faubel, R., Westendorf, C., Bodenschatz, E., & Gregor Eichele, C. (2016) · Science · doi:10.1126/science.aae0450 · Cited by 279
The rhombic lip and early cerebellar development
Wingate, R. J. T. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00177-x · Cited by 277
PV-1 is a component of the fenestral and stomatal diaphragms in fenestrated endothelia
Stan, R. V., Kubitza, M., & Palade, G. E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13203 · Cited by 272
Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis.
Fruttiger, M. (2002) · PubMed · Cited by 272
Keep, R. F., & Jones, H. C. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90163-s · Cited by 257
Rocha, S. F., Schiller, M., Jing, D., Li, H., Butz, S., Vestweber, D., Biljes, D., Drexler, H. C. A., Nieminen-Kelhä, M., Vajkoczy, P., et al. (2014) · Circulation Research · doi:10.1161/circresaha.115.304718 · Cited by 252
Muus, C., Luecken, M. D., Eraslan, G., Waghray, A., Heimberg, G., Sikkema, L., Kobayashi, Y., Vaishnav, E. D., Subramanian, A., Smilie, C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.19.049254 · Cited by 250
Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages
Mizrak, D., Levitin, H. M., Delgado, A. C., Crotet, V., Yuan, J., Chaker, Z., Silva-Vargas, V., Sims, P. A., & Doetsch, F. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.044 · Cited by 248
DeSisto, J., O’Rourke, R., Jones, H. E., Pawlikowski, B., Malek, A. D., Bonney, S., Guimiot, F., Jones, K. L., & Siegenthaler, J. A. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.06.009 · Cited by 241
Increased Extra-axial Cerebrospinal Fluid in High-Risk Infants Who Later Develop Autism
Shen, M. D., Kim, S. H., McKinstry, R. C., Gu, H., Hazlett, H. C., Nordahl, C. W., Emerson, R. W., Shaw, D., Elison, J. T., Swanson, M. R., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.02.1095 · Cited by 235
Skin-resident innate lymphoid cells converge on a pathogenic effector state
Bielecki, P., Riesenfeld, S. J., Hütter, J.-C., Triglia, E. T., Kowalczyk, M. S., Ricardo-González, R. R., Lian, M., Vesely, M. C. A., Kroehling, L., Xu, H. Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03188-w · Cited by 223
Self-citationShah, P. T., Stratton, J. A., Stykel, M. G., Abbasi, S., Sharma, S., Mayr, K. A., Koblinger, K., Whelan, P. J., & Biernaskie, J. (2018) · Cell · doi:10.1016/j.cell.2018.03.063 · Cited by 221
Regulatory Logic Underlying Diversification of the Neural Crest
Martik, M. L., & Bronner-Fraser, M. E. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.07.015 · Cited by 217
Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation
Awatramani, R., Soriano, P., Rodriguez, C., Mai, J. J., & Dymecki, S. M. (2003) · Nature Genetics · doi:10.1038/ng1228 · Cited by 215
Emergence and Developmental Roles of the Cerebrospinal Fluid System
Fame, R. M., & Lehtinen, M. K. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.01.027 · Cited by 211
Self-citationInsulin Regulates Brain Function, but How Does It Get There?
Gray, S. M., Meijer, R. I., & Barrett, E. J. (2014) · Diabetes · doi:10.2337/db14-0340 · Cited by 206
Sympathetic nervous control of cerebrospinal fluid production from the choroid plexus
Lindvall, M., Edvinsson, L., & Owman, C. (1978) · Science · doi:10.1126/science.663649 · Cited by 195
The choroid plexus is an important circadian clock component
Myung, J., Schmal, C., Hong, S., Tsukizawa, Y., Rose, P., Zhang, Y., Holtzman, M. J., Schutter, E. D., Herzel, H., Bordyugov, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03507-2 · Cited by 193
R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis
Bell, S. M., Schreiner, C. M., Wert, S. E., Mucenski, M. L., Scott, W. J., & Whitsett, J. A. (2008) · Development · doi:10.1242/dev.013359 · Cited by 191
Lun, M. P., Johnson, M. B., Broadbelt, K. G., Watanabe, M., Kang, Y., Chau, K. F., Springel, M. W., Malesz, A., Sousa, A. M. M., Pletikos, M., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3081-14.2015 · Cited by 187
Self-citationNuclei multiplexing with barcoded antibodies for single-nucleus genomics
Gaublomme, J. T., Li, B., Aubin, C., Knecht, A., Yang, Y., Drokhlyansky, E., Wittenberghe, N. V., Waldman, J., Dionne, D. A., Nguyễn, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10756-2 · Cited by 186
Self-citationTransventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development
Huang, X., Liu, J., Ketova, T., Fleming, J. T., Grover, V. K., Cooper, M. K., Litingtung, Y., & Chiang, C. C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911838107 · Cited by 167
Fleming, S. J., Chaffin, M. D., Arduini, A., Akkad, A.-D., Banks, E., Marioni, J. C., Philippakis, A. A., Ellinor, P. T., & Babadi, M. (2019) · doi:10.1101/791699 · Cited by 164
Visualizing the structure of RNA-seq expression data using grade of membership models
Dey, K. K., Hsiao, C. J., & Stephens, M. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006599 · Cited by 161
Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain
Saunders, N. R., Dzięgielewska, K. M., Møllgård, K., & Habgood, M. D. (2018) · The Journal of Physiology · doi:10.1113/jp275376 · Cited by 159
Aitkenhead, M., Wang, S., Nakatsu, M. N., Mestas, J., Heard, C. J., & Hughes, C. C. W. (2002) · Microvascular Research · doi:10.1006/mvre.2001.2380 · Cited by 149
Klotho controls the brain-immune system interface in the choroid plexus
Zhu, L., Stein, L. R., Kim, D., Ho, K., Yu, G.-Q., Zhan, L., Larsson, T. E., & Mucke, L. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1808609115 · Cited by 148
The regulation of immune cell trafficking by the extracellular matrix
Hallmann, R., Zhang, X., Russo, J. D., Li, L., Song, J., Hannocks, M., & Sorokin, L. M. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.06.006 · Cited by 140
Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development
Xu, H., Fame, R. M., Sadegh, C., Sutin, J. D. B., Naranjo, C., Syau, D., Cui, J., Shipley, F. B., Vernon, A. N., Gao, F., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20666-3 · Cited by 130
Self-citationHistogenesis of choroid plexus in man
Shuangshotĭ, S., & Netsky, M. G. (1966) · American Journal of Anatomy · doi:10.1002/aja.1001180114 · Cited by 128
Inflammation of the Embryonic Choroid Plexus Barrier following Maternal Immune Activation
Cui, J., Shipley, F. B., Shannon, M. L., Alturkistani, O., Dani, N., Webb, M. D., Sugden, A. U., Andermann, M. L., & Lehtinen, M. K. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.020 · Cited by 128
Self-citationBaskin, D. G., Woods, S. C., West, D. B., van Houten, M., Posner, B. I., Dorsa, D. M., & Porte, D. (1983) · Endocrinology · doi:10.1210/endo-113-5-1818 · Cited by 122
The choroid plexus-cerebrospinal fluid interface in Alzheimer′s disease: more than just a barrier
Vandenbroucke, R. E., Balusu, S., Brkić, M., & Libert, C. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.180372 · Cited by 119
Shipley, F. B., Dani, N., Xu, H., Deister, C., Cui, J., Head, J. P., Sadegh, C., Fame, R. M., Shannon, M. L., Flores, V. I., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.024 · Cited by 118
Self-citationCoulter, M. E., Dorobantu, C. M., Lodewijk, G. A., Delalande, F., Cianférani, S., Ganesh, V. S., Smith, R. S., Lim, E. T., Xu, C. S., Pang, S., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.06.100 · Cited by 111
Self-citationHuang, X., Ketova, T., Fleming, J. T., Wang, H., Dey, S. K., Litingtung, Y., & Chiang, C. (2009) · Development · doi:10.1242/dev.033795 · Cited by 106
Release of insulin produced by the choroid plexis is regulated by serotonergic signaling
Mazucanti, C. H., Liu, Q.-R., Lang, D., Huang, N., O’Connell, J. F., Camandola, S., & Egan, J. M. (2019) · JCI Insight · doi:10.1172/jci.insight.131682 · Cited by 101
Cross-Species Genomics Identifies TAF12, NFYC, and RAD54L as Choroid Plexus Carcinoma Oncogenes
Tong, Y., Merino, D. M., Nimmervoll, B. V., Gupta, K., Wang, Y., Finkelstein, D., Dalton, J., Ellison, D. W., Ma, X., Zhang, J., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.005 · Cited by 98
Functional roles of Lgr4 and Lgr5 in embryonic gut, kidney and skin development in mice
Kinzel, B., Pikiolek, M., Orsini, V., Sprunger, J., Isken, A., Zietzling, S., Desplanches, M., Dubost, V., Breustedt, D., Valdez, R., et al. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.03.009 · Cited by 98
Paré, A., Mailhot, B., Lévesque, S. A., Juzwik, C., Ignatius Arokia Doss, P. M., Lécuyer, M.-A., Prat, A., Rangachari, M., Fournier, A., & Lacroix, S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1714948115 · Cited by 94
Sonic hedgehog is required for vascular outgrowth in the hindbrain choroid plexus
Nielsen, C. M., & Dymecki, S. M. (2010) · Developmental Biology · doi:10.1016/j.ydbio.2010.01.032 · Cited by 89
Kaiser, K., Gyllborg, D., Procházka, J., Salašová, A., Kompaníková, P., Molina, F. L., Laguna-Goya, R., Radaszkiewicz, T., Harnoš, J., Procházková, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09298-4 · Cited by 87
Self-citationHunter, N. L., & Dymecki, S. M. (2007) · Development · doi:10.1242/dev.003095 · Cited by 83
Lack of endothelial diaphragms in fenestrae and caveolae of mutant Plvap-deficient mice
Herrnberger, L., Seitz, R., Kuespert, S., Bösl, M. R., Fuchshofer, R., & Tamm, E. R. (2012) · Histochemistry and Cell Biology · doi:10.1007/s00418-012-0987-3 · Cited by 76
Louvi, A., & Wassef, M. (2000) · Development · doi:10.1242/dev.127.18.4061 · Cited by 66
An experimental and ultrastructural study on the development of the avian choroid plexus
Wilting, J., & Christ, B. (1989) · Cell and Tissue Research · doi:10.1007/bf00218783 · Cited by 59
Mao, J., McKean, D. M., Warrier, S., Corbin, J. G., Niswander, L. A., & Zohn, I. E. (2010) · Development · doi:10.1242/dev.048744 · Cited by 54
Raphe origin of serotonin-containing neurons within choroid plexus of the rat
Moskowitz, M. A., Liebmann, J. E., Reinhard, J. F., & Schlosberg, A. J. (1979) · Brain Research · doi:10.1016/0006-8993(79)90410-4 · Cited by 53
Claudin 5 Is Transiently Expressed During the Development of the Retinal Pigment Epithelium
Kojima, S., Rahner, C., Peng, S., & Rizzolo, L. J. (2002) · The Journal of Membrane Biology · doi:10.1007/s00232-001-0137-7 · Cited by 51
Development of the lateral ventricular choroid plexus in a marsupial, Monodelphis domestica
Liddelow, S. A., Dziegielewska, K. M., VandeBerg, J. L., & Saunders, N. R. (2010) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-7-16 · Cited by 50
Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway
Chang, J. T., Lehtinen, M. K., & Sive, H. (2016) · Developmental Neurobiology · doi:10.1002/dneu.22300 · Cited by 42
Self-citationMancini, M., Greco, A., Tedeschi, E., Palma, G., Ragucci, M., Bruzzone, M. G., Coda, A. R. D., Torino, E., Scotti, A., Zucca, I., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129912 · Cited by 36
Hagan, N., & Zervas, M. (2011) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2011.11.008 · Cited by 35
Mice Expressing Myc in Neural Precursors Develop Choroid Plexus and Ciliary Body Tumors
Shannon, M. L., Fame, R. M., Chau, K. F., Dani, N., Calicchio, M. L., Géléoc, G. S. G., Lidov, H. G. W., Alexandrescu, S., & Lehtinen, M. K. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.02.009 · Cited by 25
Self-citationDo genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia
Palha, J. A., Santos, N. C., Marques, F., Sousa, J. C., Bessa, J. M., Miguelote, R. F. O., Sousa, N., & Belmonte-de-Abreu, P. S. (2012) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2012.00031 · Cited by 21
Bielecki, P., Riesenfeld, S. J., Kowalczyk, M. S., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/461228 · Cited by 21
Self-citationThe development of the vascular pattern of the choroid plexus of the lateral ventricles
Hudson, A. J. (1960) · Journal of Comparative Neurology · doi:10.1002/cne.901150206 · Cited by 15
Comment on “Multiple repressive mechanisms in the hippocampus during memory formation”
Mathew, R. S., Mullan, H., Blusztajn, J. K., & Lehtinen, M. K. (2016) · Science · doi:10.1126/science.aaf1288 · Cited by 15
Self-citationThe line between science and politics
Weintraub, M. (2016) · Science · doi:10.1126/science.aah3551 · Cited by 5
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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