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

Single-Cell Transcriptomic Analyses of the Developing Meninges Reveal Meningeal Fibroblast Diversity and Function.
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DOI:
10.1016/j.devcel.2020.06.009
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发表时间:
2020-07-06
期刊:
影响因子:
11.8
通讯作者:
Siegenthaler JA
Siegenthaler JA
中科院分区:
生物学1区
文献类型:
--
作者:
DeSisto J;O'Rourke R;Jones HE;Pawlikowski B;Malek AD;Bonney S;Guimiot F;Jones KL;Siegenthaler JA

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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 pial. 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. DeSisto et al. use scRNA-seq to create a molecular profile of developing mouse meningeal fibroblasts. They show that fibroblasts of the pia, arachnoid, and dura meningeal layers are transcriptionally distinct, some layer markers are conserved in human fetal meninges, and fibroblast subsets demonstrate brain region-localized gene expression.
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