A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function
A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function
Abstract The meninges, a multilayered structure that encases the CNS, is composed mostly of fibroblasts, along with vascular and immune cells. Meningeal fibroblasts are a vital source of signals that control neuronal migration and neurogenesis yet strikingly little is known about their development. We used single cell RNA sequencing to generate a cellular atlas of embryonic meningeal fibroblasts in control and Foxc1-KO mice in which severe CNS defects arise from failed meningeal fibroblast development. We report unique transcriptional signatures for dura, arachnoid and pial fibroblasts and identify S100a6 as the first unique marker of the pial layer. We describe a new meningeal fibroblast subtype marked by μ-Crystallin expression and show these cell types and markers are conserved in human fetal meninges. Our analysis demonstrates layer specific production of extracellular matrix components, transporter expression, and synthesis of secreted factors. Lastly, the cellular atlas of Foxc1-KO meninges provides insight into their severe phenotype, confirming a massive loss in arachnoid and dura fibroblasts and Foxc1-KO pial fibroblasts are so altered that they cluster as a different cell type based on gene expression. These studies provide an unprecedented view of meningeal fibroblast development, highlighting unexpected fibroblast diversity and function, while providing mechanistic insights into the meninges role in CNS development.
O?ˉRourke Rebecca、DeSisto John、Jones Hannah E.、Jones Kenneth L.、Guimiot Fabien、Siegenthaler Julie A.、Bonney Stephanie
Department of Pediatrics Section of Section of Hematology, Oncology, Bone Marrow Transplant, University of ColoradoDepartment of Pediatrics Section of Developmental Biology, University of Colorado||Department of Pediatrics Section of Section of Hematology, Oncology, Bone Marrow Transplant, University of Colorado||Cell Biology, Stem Cells and Development Graduate Program, University of ColoradoDepartment of Pediatrics Section of Developmental Biology, University of Colorado||Cell Biology, Stem Cells and Development Graduate Program, University of ColoradoDepartment of Pediatrics Section of Section of Hematology, Oncology, Bone Marrow Transplant, University of ColoradoINSERM UMR 1141, H?pital Robert Debr¨|Department of Pediatrics Section of Developmental Biology, University of Colorado||Cell Biology, Stem Cells and Development Graduate Program, University of ColoradoDepartment of Pediatrics Section of Developmental Biology, University of Colorado||Cell Biology, Stem Cells and Development Graduate Program, University of Colorado
基础医学细胞生物学神经病学、精神病学
brain developmentmeningespial basement membraneretinoic acidhuman meninges
O?ˉRourke Rebecca,DeSisto John,Jones Hannah E.,Jones Kenneth L.,Guimiot Fabien,Siegenthaler Julie A.,Bonney Stephanie.A cellular atlas of the developing meninges reveals meningeal fibroblast diversity and function[EB/OL].(2025-03-28)[2025-07-02].https://www.biorxiv.org/content/10.1101/648642.点此复制
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