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bioRxiv · 10.1101/2024.05.12.593751

Embryonic diversification of adult neural stem cells and ependymal cells

Yamaguchi, S.·Kuniya, T.·Omiya, H.·Suzuki, Y.·Seki, M.·Ukai, H.·Fang, L.·Harada, Y.·Kawaguchi, D.·Gotoh, Y.
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Abstract

Both adult neural stem (type B) cells and ependymal (type E) cells in the mouse ventricular-subventricular zone (V-SVZ) are derived from slowly dividing (or quiescent) embryonic neural stem-progenitor cells (NPCs) that are set aside during development. However, it has remained unclear whether fate diversification between adult type B and type E cells actually occurs during embryogenesis. Here we performed single-cell transcriptomic analysis of slowly dividing embryonic NPCs and identified cell subpopulations transcriptionally similar to adult type B or type E cells. The type B- like embryonic cells appeared to emerge before embryonic day (E) 13.5, whereas the type E-like cells became evident between E13.5 and E16.5. Genes differentially expressed in B-like embryonic cells (versus E-like cells) included Tmem100, Cadm2, and bone morphogenetic protein (BMP)-induced genes. Forced expression of an active form of BMP receptor (ALK2QD), TMEM100, or CADM2 in embryonic NPCs resulted in preferential generation of adult type B cells relative to type E cells in the postnatal brain. Moreover, knockdown of TMEM100 resulted in relative enrichment of type E cells over type B cells. Our results indicate that the embryonic origin of adult type B cells and that of type E cells have already diverged molecularly during embryogenesis, and they have identified key molecular players in this fate bifurcation.

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Yamaguchi, S., Kuniya, T., Omiya, H., Suzuki, Y., Seki, M., Ukai, H., Fang, L., Harada, Y., Kawaguchi, D., Gotoh, Y.. 2024-05-14. Embryonic diversification of adult neural stem cells and ependymal cells. https://doi.org/10.1101/2024.05.12.593751

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