Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.
Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.
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DOI：
10.1126/science.aaf4802
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发表时间：
2016-07-15
期刊：
影响因子：
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通讯作者：
Guillemot F
中科院分区：
文献类型：
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作者：
Urbán N;van den Berg DL;Forget A;Andersen J;Demmers JA;Hunt C;Ayrault O;Guillemot F
静止对于成体干细胞的长期维持至关重要。小生境信号调节干细胞从休眠状态到激活状态的过渡。在这里，我们发现e3 -泛素连接酶Huwe1 （HECT， UBA和WWE结构域包含1）是成年小鼠海马增殖干细胞恢复静止所必需的。Huwe1破坏增殖海马干细胞中的促激活蛋白Ascl1（毛囊鳞状细胞家族bHLH转录因子1）的稳定性，从而阻止细胞周期蛋白Ds的积累并促进其恢复到静息状态。当干细胞不能恢复到静止状态时，增殖干细胞池就会枯竭。因此，海马神经发生的长期维持依赖于干细胞通过一种关键激活因子的快速降解而恢复到短暂的静止状态。
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 destabilises pro-activation 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 activation factor.