Proceedings of the National Academy of Sciences of the United States of America · 2018
Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Basak Onur, Krieger Teresa G, Muraro Mauro J, Wiebrands Kay, Stange Daniel E, Frias-Aldeguer Javier, Rivron Nicolas C, van de Wetering Marc, van Es Johan H, van Oudenaarden Alexander, Simons Benjamin D, Clevers Hans
Аннотация
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 Ki67iresCreER 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.