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. |