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JOURNAL ARTICLE

Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy

Onur Basak, Teresa G Krieger, Mauro J Muraro, Kay Wiebrands, Daniel E Stange, Javier Frias-Aldeguer, Nicolas C Rivron, Marc van de Wetering, Johan H van Es, Alexander van Oudenaarden, Benjamin D Simons, Hans Clevers
Proceedings of the National Academy of Sciences of the United States of America 2018 January 23, 115 (4): E610-E619
29311336
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.

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