Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages

成人 V-SVZ 神经干细胞谱系区域差异的单细胞分析

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作者:Dogukan Mizrak, Hanna Mendes Levitin, Ana C Delgado, Valerie Crotet, Jinzhou Yuan, Zayna Chaker, Violeta Silva-Vargas, Peter A Sims, Fiona Doetsch

Abstract

The ventricular-subventricular zone (V-SVZ) harbors adult neural stem cells. V-SVZ neural stem cells exhibit features of astrocytes, have a regional identity, and depending on their location in the lateral or septal wall of the lateral ventricle, generate different types of neuronal and glial progeny. We performed large-scale single-cell RNA sequencing to provide a molecular atlas of cells from the lateral and septal adult V-SVZ of male and female mice. This revealed regional and sex differences among adult V-SVZ cells. We uncovered lineage potency bias at the single-cell level among lateral and septal wall astrocytes toward neurogenesis and oligodendrogenesis, respectively. Finally, we identified transcription factor co-expression modules marking key temporal steps in neurogenic and oligodendrocyte lineage progression. Our data suggest functionally important spatial diversity in neurogenesis and oligodendrogenesis in the adult brain and reveal molecular correlates of adult NSC dormancy and lineage specialization.

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