Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Kyoto University Graduate School of Biostudies, Kyoto, Japan.
Dev Growth Differ. 2020 Jan;62(1):59-66. doi: 10.1111/dgd.12626. Epub 2019 Sep 6.
Somatic stem/progenitor cells actively proliferate and give rise to different types of mature cells (active state) in embryonic tissues while they are mostly dormant (quiescent state) in many adult tissues. Notch signaling is known to regulate both active and quiescent states of somatic stem cells, but how it regulates these different states is unknown. Recent studies revealed that the Notch effector Hes1 is expressed differently during the active and quiescent states during neurogenesis and myogenesis: high in the quiescent state and oscillatory in the active state. When the Hes1 expression level is high, both Ascl1 and MyoD expression are continuously suppressed. By contrast, when Hes1 expression oscillates, it periodically represses expression of the neurogenic factor Ascl1 and the myogenic factor MyoD, thereby driving Ascl1 and MyoD oscillations. High levels of Hes1 and the resultant Ascl1 suppression promote the quiescent state of neural stem cells, while Hes1 oscillation-dependent Ascl1 oscillations regulate their active state. Similarly, in satellite cells of muscles, known adult muscle stem cells, high levels of Hes1 and the resultant MyoD suppression seem to promote their quiescent state, while Hes1 oscillation-dependent MyoD oscillations activate their proliferation and differentiation. Therefore, the expression dynamics of Hes1 is a key regulatory mechanism of generating and maintaining active/quiescent stem cell states.
体干细胞/祖细胞在胚胎组织中积极增殖并产生不同类型的成熟细胞（活跃状态），而在许多成年组织中它们大多处于休眠状态（静止状态）。 Notch 信号通路已知可调节体干细胞的活跃状态和静止状态，但它如何调节这些不同状态尚不清楚。最近的研究表明，Notch 效应因子 Hes1 在神经发生和肌发生过程中的活跃状态和静止状态下表达不同：在静止状态下高表达，在活跃状态下呈振荡表达。当 Hes1 表达水平较高时，Ascl1 和 MyoD 的表达均被持续抑制。相比之下，当 Hes1 表达呈振荡状态时，它会周期性地抑制神经发生因子 Ascl1 和肌生成因子 MyoD 的表达，从而驱动 Ascl1 和 MyoD 的振荡。高水平的 Hes1 和由此产生的 Ascl1 抑制促进神经干细胞的静止状态，而 Hes1 振荡依赖性的 Ascl1 振荡调节其活跃状态。同样，在肌肉中的卫星细胞（已知的成年肌肉干细胞）中，高水平的 Hes1 和由此产生的 MyoD 抑制似乎促进其静止状态，而 Hes1 振荡依赖性的 MyoD 振荡激活其增殖和分化。因此，Hes1 的表达动态是产生和维持活跃/静止干细胞状态的关键调节机制。
