Single cell sequencing of the hippocampal niche. 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. Overall design: We generated transciptome data from cells unbiasely sorted from the hippocampal neurogenic niche after depleting the neuronal population

小鼠齿状回的成年神经发生（adult neurogenesis）发生于特化的微环境中，该微环境可终生维持神经元的产生。为全面阐明成年神经发生的调控机制，明确神经干细胞（neural stem cell, NSC）与祖细胞的发育阶段、其分子决定因素，以及微环境的细胞与分子组成是至关重要的。本研究针对海马神经源性微环境开展了单细胞RNA测序（single cell RNA sequencing）分析，实验过程中分离了所有非神经元细胞群。本分析全面刻画了齿状回细胞的整体特征，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特征，研究发现神经干细胞呈现异质性的细胞连续谱系，而祖细胞可被划分为不同的亚型。我们解析了少突胶质细胞谱系及其转录动态特征，并刻画了小胶质细胞的转录组谱与激活状态。本研究整合所得的数据集可为阐明成年神经发生的调控机制提供宝贵的研究资源。实验设计概述：我们在去除神经元群体后，从海马神经源性微环境中无偏分选细胞，并由此生成了转录组数据。