Format

Send to

Choose Destination
Science. 2016 Jul 15;353(6296):292-5. doi: 10.1126/science.aaf4802.

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

Author information

1
The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK. noelia.urban@crick.ac.uk francois.guillemot@crick.ac.uk.
2
The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK.
3
Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France. Université Paris Sud, Université Paris Saclay, CNRS UMR 3347, INSERM U1021, 91405, Orsay, France.
4
Proteomics Center, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, Netherlands.

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.

PMID:
27418510
PMCID:
PMC5321528
DOI:
10.1126/science.aaf4802
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center