期刊
SCIENCE
卷 353, 期 6296, 页码 292-295出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf4802
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资金
- Medical Research Council (MRC)
- Francis Crick Institute [BZ10089]
- Federation of European Biochemical Societies
- Netherlands Organisation for Scientific Research (NWO) [184.032.201]
- Fondation de France
- Wellcome Trust [106187/Z/14/Z]
- Biotechnology and Biological Sciences Research Council [BB/K005316/1]
- MRC [U117570528]
- Wellcome Trust [106187/Z/14/Z] Funding Source: Wellcome Trust
- BBSRC [BB/K005316/1] Funding Source: UKRI
- MRC [MC_U117570528, MR/M023907/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K005316/1] Funding Source: researchfish
- Medical Research Council [MC_U117570528, MR/M023907/1] Funding Source: researchfish
- The Francis Crick Institute [10309, 10089] Funding Source: researchfish
- Wellcome Trust [106187/Z/14/Z] Funding Source: researchfish
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.
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