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

• Autores: Noelia Urbán, Antoine Forget, Jimena Andersen, Charles Hunt
• Localización: Science, ISSN 0036-8075, Vol. 353, Nº 6296, 2016, págs. 292-295
• Idioma: inglés
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• Resumen

  • 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.