Eli and Edythe Broad Institute for Stem Cell Research and Regeneration Medicine, University of California, San Francisco, San Francisco, United States.
Department of Neurological Surgery, University of California, San Francisco, San Francisco, United States.
Elife. 2021 Jul 14;10:e67436. doi: 10.7554/eLife.67436.
The ventricular-subventricular zone (V-SVZ), on the walls of the lateral ventricles, harbors the largest neurogenic niche in the adult mouse brain. Previous work has shown that neural stem/progenitor cells (NSPCs) in different locations within the V-SVZ produce different subtypes of new neurons for the olfactory bulb. The molecular signatures that underlie this regional heterogeneity remain largely unknown. Here, we present a single-cell RNA-sequencing dataset of the adult mouse V-SVZ revealing two populations of NSPCs that reside in largely non-overlapping domains in either the dorsal or ventral V-SVZ. These regional differences in gene expression were further validated using a single-nucleus RNA-sequencing reference dataset of regionally microdissected domains of the V-SVZ and by immunocytochemistry and RNAscope localization. We also identify two subpopulations of young neurons that have gene expression profiles consistent with a dorsal or ventral origin. Interestingly, a subset of genes are dynamically expressed, but maintained, in the ventral or dorsal lineages. The study provides novel markers and territories to understand the region-specific regulation of adult neurogenesis.
脑室下区 (V-SVZ) 位于侧脑室壁上,是成年小鼠大脑中最大的神经发生龛。先前的研究表明,V-SVZ 内不同位置的神经干细胞/祖细胞 (NSPC) 产生嗅球的不同亚型新神经元。这种区域异质性的分子特征在很大程度上尚不清楚。在这里,我们展示了成年小鼠 V-SVZ 的单细胞 RNA 测序数据集,揭示了两种 NSPC 群体,它们主要位于 V-SVZ 的背侧或腹侧非重叠区域。这些区域在基因表达上的差异进一步通过对 V-SVZ 区域微分离区域的单个核 RNA 测序参考数据集的验证,以及免疫细胞化学和 RNAscope 定位来验证。我们还鉴定了两种具有与背侧或腹侧起源一致的基因表达谱的年轻神经元亚群。有趣的是,一组基因在腹侧或背侧谱系中动态表达,但仍保持表达。该研究提供了新的标记和领域,以了解成年神经发生的区域特异性调控。