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

First Author  Basak O Year  2018
Journal  Proc Natl Acad Sci U S A Volume  115
Issue  4 Pages  E610-E619
PubMed ID  29311336 Mgi Jnum  J:254891
Mgi Id  MGI:6113348 Doi  10.1073/pnas.1715911114
Citation  Basak O, et al. (2018) Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy. Proc Natl Acad Sci U S A 115(4):E610-E619
abstractText  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.
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