Return to quiescence of mouse neural stem cells by degradation of a proactivation protein

Journal Article: ScienceYear Published: (2016) Volume Number: 353, Article Number: 292-295


Urbán,Noelia; van den Berg,Debbie LC; Forget,Antoine; Andersen,Jimena; Demmers,Jeroen AA; Hunt,Charles; Ayrault,Olivier; Guillemot,François

Quiescence is essential for long-term maintenance of adult stem cells. Niche signals regulate the transit of stem cells from dormant to activated states. Here, we show that the E3-ubiquitin ligase Huwe1 (HECT, UBA, and WWE domain-containing 1) is required for proliferating stem cells of the adult mouse hippocampus to return to quiescence. Huwe1 destabilizes proactivation protein Ascl1 (achaete-scute family bHLH transcription factor 1) in proliferating hippocampal stem cells, which prevents accumulation of cyclin Ds and promotes the return to a resting state. When stem cells fail to return to quiescence, the proliferative stem cell pool becomes depleted. Thus, long-term maintenance of hippocampal neurogenesis depends on the return of stem cells to a transient quiescent state through the rapid degradation of a key proactivation factor.