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

N Urban, DLC van den Berg, A Forget, J Andersen, Jeroen Demmers, C Hunt, O Ayrault, F Guillemot

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Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)292-295
Number of pages4
JournalScience
Volume353
Issue number6296
DOIs
Publication statusPublished - 2016

Research programs

  • EMC MGC-02-21-01

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