Troy plus brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy
Troy plus brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy
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DOI：
10.1073/pnas.1715911114
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发表时间：
2018-01-23
影响因子：
11.1
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
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作者：
Basak, Onur;Krieger, Teresa G.;Clevers, Hans
成年小鼠室管膜下区为哺乳动物神经干细胞（NSCs）提供了一个小生境。然而，神经干细胞的分子特征，自我更新潜力和命运行为仍然不清楚。在这里，我们提出了一个模型，其中活跃的神经干细胞的命运是耦合到一个共享的生态位中的相邻神经干细胞的总数。使用敲入报告等位基因和单细胞RNA测序，我们表明，Wnt靶Tnfrsf 19/特洛伊识别活跃和静止的神经干细胞。对个体神经干细胞的遗传谱系追踪的定量分析显示，在恢复到静止状态之前，干细胞数量迅速扩增。这种行为最好用随机命运决定来解释，即共享小生境内的干细胞数量随时间波动。使用Ki 67（iresCreER）等位基因对增殖细胞进行命运作图证实了活性NSC可逆地恢复到静止状态，实现长期自我更新。我们的研究结果表明，一个利基为基础的机制，调节神经干细胞的命运和数量。
The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67(iresCreER) allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.