Single cell sequencing of the hippocampal niche

Adult neurogenesis in the murine dentate gyrus occurs in a specialized microenvironment that sustains the generation of neurons during life. To fully understand adult neurogenesis, it is essential to determine the neural stem cell (NSC) and progenitor developmental stages, their molecular determinants, and the niche cellular and molecular composition. We report on a single cell RNA sequencing study of the hippocampal niche, performed by isolating all the non-neuronal cell populations. Our analysis provides a comprehensive description of the dentate gyrus cells and allows the identification of exclusive cell type-specific markers. We define the developmental stages and transcriptional dynamics of NSCs and progenitors, and find that while NSCs represent a heterogeneous cellular continuum, progenitors can be grouped in distinct subtypes. We determine the oligodendrocyte lineage and transcriptional dynamics, and describe microglia transcriptional profile and activation state. The combined data constitutes a valuable resource to understand regulatory mechanisms of adult neurogenesis. We generated transciptome data from cells unbiasely sorted from the hippocampal neurogenic niche after depleting the neuronal population小鼠齿状回中的成年神经发生（Adult neurogenesis）发生于一个特定微环境中，该微环境可在生物体整个生命周期中维持神经元的产生。为全面阐明成年神经发生的机制，明确神经干细胞（NSC，neural stem cell）与祖细胞的发育阶段、其分子决定因子，以及该微环境的细胞与分子组成至关重要。 本研究报道了一项针对海马神经微环境的单细胞RNA测序（single cell RNA sequencing）研究：我们通过分离所有非神经元细胞群完成了该实验。我们的分析实现了对齿状回细胞的全面表征，并可鉴定出专属的细胞类型特异性标志物。我们明确了神经干细胞与祖细胞的发育阶段及转录动态，且发现尽管神经干细胞构成异质性细胞连续体，但祖细胞可被划分为不同亚型。我们解析了少突胶质细胞谱系及其转录动态，并描述了小胶质细胞的转录谱与激活状态。本整合数据集为阐明成年神经发生的调控机制提供了宝贵的研究资源。我们还通过在清除神经元群体后，从海马神经发生微环境中对细胞进行无偏分选，获取了其转录组数据。