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

Abstract

Significance Adult mammalian tissues contain stem cells that contribute to tissue homeostasis and regeneration, with potential therapeutic applications. Specialized niches regulate their fate. Here we evaluated quantitatively how the subependymal zone niche regulates neural stem cell (NSC) number in the adult mouse brain. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/ Troy identifies both active and quiescent NSCs. Using the Ki67-iresCreER mouse model, we found that dividing stem cells have long-term self-renewal potential. We propose a model where the fate of NSCs is coupled to their density within a closed niche. Our results suggest a new mechanism for regulating adult stem cell number, which might be deregulated in brain malignancies and in aging.