Single-cell transcriptomic analyses of the developing meninges reveal meningeal fibroblast diversity and function.
Open accessAbstract
The meninges are a multilayered structure composed of fibroblasts, blood and lymphatic vessels, and immune cells. Meningeal fibroblasts secrete a variety of factors that control CNS development, yet strikingly little is known about their heterogeneity or development. Using single-cell sequencing, we report distinct transcriptional signatures for fibroblasts in the embryonic dura, arachnoid, and pia. We define new markers for meningeal layers and show conservation in human meninges. We find that embryonic meningeal fibroblasts are transcriptionally distinct between brain regions and identify a regionally localized pial subpopulation marked by the expression of μ-crystallin. Developmental analysis reveals a progressive, ventral-to-dorsal maturation of telencephalic meninges. Our studies have generated an unparalleled view of meningeal fibroblasts, providing molecular profiles of embryonic meningeal fibroblasts by layer and yielding insights into the mechanisms of meninges development and function.
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The pia is collagen and basement membrane-rich, abuts the glial limitans, and has regional heterogeneity within the developing mouse brain.
“Most proximate to the brain is the collagen and basement membrane-rich pia matter that abuts the glial limitans and has recently be shown to have regional heterogeneity within the developing mouse brain.”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as DeSisto et al., 2020
Arachnoid barrier cells are epithelial-like cells connected by tight and adherens junctions that regulate the movement of pathogens, molecules, and cells into and out of the CSF and brain parenchyma.
“Segregating the outer and inner meningeal compartments is the epithelial-like arachnoid barrier cells, connected by tight and adherens junctions, which regulate the movement of pathogens, molecules, and cells into and out of the cerebral spinal fluid (CSF) and brain parenchyma.”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as DeSisto et al., 2020
Arachnoid barrier cells can be first seen in the mouse forebrain around E13 and they differentiate from mesenchymal cells of the primary meninx.
“We recently found that arachnoid barrier cells can be first seen in the mouse forebrain around E13 and they differentiate from mesenchymal cells of the primary meninx (DeSisto et al., 2020).”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as DeSisto et al., 2020
Arachnoid fibroblasts express RALDH2 and CRABP2, a retinoic acid (RA) synthesizing enzyme and an RA binding protein, respectively.
“Arachnoid fibroblasts express RALDH2 and CRABP2, a retinoic acid (RA) synthesizing enzyme and an RA binding protein, respectively (Figures 1D,E; DeSisto et al., 2020).”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as DeSisto et al., 2020
Our recent scRNAseq of developing mouse meninges showed pia, arachnoid and dura fibroblasts are molecularly distinct and likely have layer specific functions.
“Our recent single cell RNA sequencing (scRNAseq) of developing mouse meninges showed pia, arachnoid and dura fibroblasts are molecularly distinct and likely have layer specific functions (DeSisto et al., 2020).”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as DeSisto et al., 2020
3V ChP fibroblasts shared expression signatures with meningeal fibroblasts and the ceiling cell fibroblast subtype.
“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).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as DeSisto et al., 2020
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- Authors
- DeSisto, J., O’Rourke, R., Jones, H. E., Pawlikowski, B., Malek, A. D., Bonney, S., Guimiot, F., Jones, K. L., & Siegenthaler, J. A.
- Affiliations
- University of Colorado Anschutz (US)
- Inserm (FR)
- Corresponding author
- Siegenthaler, Julie A.
- ORCID
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 54
- Issue
- 1
- Pages
- 43-59.e4
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC7769050
- OpenAlex
- W3038769421
- Cited by
- 241
- References
- 64
- Citations by year
- 2026: 42 · 2025: 49 · 2024: 43 · 2023: 43 · 2022: 35 · 2021: 23 · 2020: 5 · 2019: 1
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R03 NS104566, R01 NS098273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- meningeal fibroblasts, dura mater, arachnoid, pia mater, fibroblast heterogeneity, telencephalon, central nervous system development
- MeSH terms
- RNA-Seq, Animals, Brain, Crystallins, Fibroblasts, Humans, Meninges, Mice, Inbred C57BL, Mice, Single-Cell Analysis, Transcriptome
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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