Single-Cell Transcriptomic Analyses of the Developing Meninges Reveal Meningeal Fibroblast Diversity and Function

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...

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Published inDevelopmental cell Vol. 54; no. 1; pp. 43 - 59.e4
Main Authors DeSisto, John, O’Rourke, Rebecca, Jones, Hannah E., Pawlikowski, Bradley, Malek, Alexandra D., Bonney, Stephanie, Guimiot, Fabien, Jones, Kenneth L., Siegenthaler, Julie A.
Format Journal Article
LanguageEnglish
Published United States 06.07.2020
Subjects
Animals
Brain - cytology
Brain - embryology
Brain - metabolism
Crystallins - genetics
Crystallins - metabolism
Fibroblasts - metabolism
Humans
Meninges - cytology
Meninges - embryology
Meninges - metabolism
Mice
Mice, Inbred C57BL
RNA-Seq
Single-Cell Analysis
Transcriptome
arachnoid barrier
brain development
retinoic acid
scRNA-seq
fibroblast
human meninges
CNS
pial basement membrane
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Summary: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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AUTHOR CONTRIBUTIONS
Conceptualization, J.D. and J.A.S.; Methodology, J.D., H.E.J., S.B., and J.A.S.; Formal Analysis, J.D., R.O., K.L.J., and J.A.S.; Investigation, J.D., H.E.J., A.D.M., B.P., and J.A.S.; Data Curation, J.D. and R.O.; Resources, F.G.; Writing–Original Draft, J.D., R.O., H.E.J., B.P., and J.A.S.; Writing–Review & Editing, J.D., R.O., H.E.J., B.P., and J.A.S.; Visualization, J.D., R.O., H.E.J., and J.A.S.; Supervision, J.A.S.; Project Administration, J.A.S.; Funding Acquisition, J.A.S.
ISSN:1534-5807
1878-1551
1878-1551
DOI:10.1016/j.devcel.2020.06.009