通过降解一种促激活蛋白使小鼠神经干细胞恢复静止状态。
Return to quiescence of mouse neural stem cells by degradation of a proactivation protein.
作者信息
Urbán Noelia, van den Berg Debbie L C, Forget Antoine, Andersen Jimena, Demmers Jeroen A A, Hunt Charles, Ayrault Olivier, Guillemot François
机构信息
The Francis Crick Institute-Mill Hill Laboratory, NW7 1AA, London, UK.
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.
出版信息
Science. 2016 Jul 15;353(6296):292-5. doi: 10.1126/science.aaf4802.
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.
静止状态对于成体干细胞的长期维持至关重要。微环境信号调节干细胞从休眠状态到激活状态的转变。在此，我们表明E3泛素连接酶Huwe1（含HECT、UBA和WWE结构域的1）是成年小鼠海马体增殖干细胞恢复静止状态所必需的。Huwe1使增殖性海马体干细胞中的促激活蛋白Ascl1（无翅型MMTV整合位点家族bHLH转录因子1）不稳定，这可防止细胞周期蛋白D的积累并促进恢复到静止状态。当干细胞无法恢复静止状态时，增殖性干细胞池就会耗尽。因此，海马体神经发生的长期维持取决于通过关键促激活因子的快速降解使干细胞恢复到短暂的静止状态。
Zotero 插件