Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany.
Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin-Buch, Germany.
Cell Rep. 2018 Nov 27;25(9):2457-2469.e8. doi: 10.1016/j.celrep.2018.11.003.
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.
神经干细胞 (NSCs) 有助于大脑的可塑性和修复。含有 NSCs 的龛位调节干细胞的自我更新和分化。我们使用全面和非靶向的单细胞 RNA 谱分析，生成了成年小鼠大脑最大生殖区域 - 侧脑室下区 (SVZ) 的分子细胞图谱。我们对 >20 种神经和非神经细胞类型进行了特征描述，并通过基于 RNA 动力学的计算分析预测未来的细胞状态，深入了解神经发生的动态。此外，我们还应用单细胞方法记录了 LRP2 缺失小鼠的 NSCs 数量减少、祖细胞增殖活性降低以及 Wnt 和 BMP 信号通路紊乱的情况，LRP2 是 SVZ 维持所必需的内吞受体。我们的数据为研究成年神经发生提供了有价值的资源，并证明了单细胞 RNA 测序在阐明功能丧失模型中神经细胞类型特异性改变方面的强大功能。
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