Otsuki L, Brand A H
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Science. 2018 Apr 6;360(6384):99-102. doi: 10.1126/science.aan8795.
Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G or G G-G heterogeneity directs NSC behavior: G qNSCs reactivate before G qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G NSCs to enter quiescence by promoting degradation of Cdc25 and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.
成体组织中的静止干细胞可被激活以维持体内平衡或进行修复。大脑中的神经干细胞（NSCs）会通过胰岛素信号通路响应营养从静止状态重新激活。普遍认为静止干细胞停滞在G期。然而，在本研究中，我们证明静止神经干细胞（qNSCs）停滞在G1或G2期。G1-G2异质性指导神经干细胞行为：G1期qNSCs比G2期qNSCs更早重新激活。此外，我们表明进化上保守的假激酶Tribbles（Trbl）通过促进Cdc25降解诱导G2期神经干细胞进入静止状态，随后通过抑制Akt激活维持静止状态。胰岛素信号通路克服对Akt的抑制并使Trbl转录沉默，使神经干细胞退出静止状态。我们的结果对于识别和操纵静止干细胞用于再生目的具有重要意义。
