Single-cell transcriptomics characterizes cell types in the subventricular zone and uncovers molecular defects impairing adult neurogenesis.

Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs regulate stem cell self-renewal and differentiation. We used comprehensive and untargeted single-cell RNA profiling to generate a molecular cell atlas of the largest germinal region of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we applied our single-cell approach to document decreased numbers of NSCs, reduced proliferation activity of progenitors, and perturbations in Wnt and BMP signaling pathways in mice lacking LRP2, an endocytic receptor required for SVZ maintenance. Our data provide a valuable resource to study adult neurogenesis and a proof-of-principle for the power of single-cell RNA-sequencing to elucidate neural cell type-specific alterations in loss-of-function models. We subjected cells derived from the adult subventricular zone neurogenic niche to single-cell RNA sequencing without pre-selection and sorting.神经干细胞（Neural stem cells, NSCs）参与成年大脑的可塑性维持与损伤修复。包裹神经干细胞的干细胞微环境调控干细胞的自我更新与分化过程。本研究采用全面无偏向性的单细胞RNA谱分析技术，构建了成年小鼠大脑最大生发区域——侧脑室下区（subventricular zone, SVZ）的分子细胞图谱。研究团队鉴定表征了超过20种神经细胞与非神经细胞类型，并通过对RNA动力学的计算分析预测细胞未来状态，深入解析了神经发生的动态过程。此外，本研究利用该单细胞分析方法，记录了LRP2（一种维持侧脑室下区稳态的内吞受体）敲除小鼠中神经干细胞数量减少、祖细胞增殖活性降低，以及Wnt与BMP信号通路异常扰动的现象。本研究数据为成年神经发生的相关研究提供了宝贵资源，同时验证了单细胞RNA测序技术在解析功能缺失模型中神经细胞类型特异性改变方面的应用价值。本研究对直接取自成年侧脑室下区神经发生微环境的细胞未进行预先筛选与分选，直接开展了单细胞RNA测序。