Staging quiescent cells Tissue-specific stem cells either divide or wait in a quiescent state until needed by the body. Quiescent stem cells have been thought to reside in the G0 stage before activating to reenter the cell cycle. However, Otsuki and Brand now show that most quiescent stem cells in the Drosophila brain are arrested in G2. Cells in the two phases display differences; for example, G2 stem cells awaken more quickly than G0 stem cells, with the conserved pseudokinase Tribbles playing a regulatory role. Elucidating the different pathways and mechanisms underlying quiescence could help to inform regenerative drug design. Science, this issue p. 99 G2-arrested quiescent stem cells reactivate more readily than G0 cells and are regulated by the pseudokinase Tribbles. Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0. In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0. G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

中文翻译：

---

细胞周期异质性指导神经干细胞从静止激活的时间

对静止细胞进行分期 组织特异性干细胞要么分裂要么在静止状态下等待，直到身体需要。静止干细胞被认为在激活以重新进入细胞周期之前处于 G0 阶段。然而，Otsuki 和 Brand 现在表明，果蝇大脑中的大多数静止干细胞都在 G2 中停滞。两相细胞显示差异；例如，G2 干细胞比 G0 干细胞苏醒得更快，保守的假激酶 Tribbles 起着调节作用。阐明静止的不同途径和机制可能有助于为再生药物设计提供信息。科学，这个问题 p。99 G2 停滞的静止干细胞比 G0 细胞更容易重新激活，并受假激酶 Tribbles 的调节。成人组织中的静止干细胞可以被激活以实现体内平衡或修复。果蝇中的神经干细胞 (NSC) 通过胰岛素信号通路从静止状态重新激活以响应营养。人们普遍认为，静止干细胞在 G0 期停滞。然而，在这项研究中，我们证明静止的 NSCs (qNSCs) 在 G2 或 G0 中被逮捕。G2-G0 异质性指导 NSC 行为：G2 qNSCs 在 G0 qNSCs 之前重新激活。此外，我们表明进化上保守的假激酶 Tribbles (Trbl) 通过促进 Cdc25String 的降解诱导 G2 NSCs 进入静止状态，随后它通过抑制 Akt 激活来维持静止状态。胰岛素信号超越了 Akt 的抑制并使 trbl 转录沉默，从而允许 NSC 退出静止状态。