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The significance of gene expression dynamics in neural stem cell regulation
Proceedings of the Japan Academy, Series B ( IF 4.4 ) Pub Date : 2020-10-09 , DOI: 10.2183/pjab.96.026
Ryoichiro Kageyama 1, 2, 3, 4 , Shohei Ochi 1, 2, 5 , Risa Sueda 1, 3 , Hiromi Shimojo 1, 6
Affiliation  

Neural stem cells (NSCs) actively proliferate and generate neurons and glial cells (active state) in the embryonic brain, whereas they are mostly dormant (quiescent state) in the adult brain. The expression dynamics of Hes1 are different between active and quiescent NSCs. In active NSCs, Hes1 expression oscillates and periodically represses the expression of proneural genes such as Ascl1, thereby driving their oscillations. By contrast, in quiescent NSCs, Hes1 oscillations maintain expression at higher levels even at trough phases (thus continuous), thereby continuously suppressing proneural gene expression. High levels of Hes1 expression and the resultant suppression of Ascl1 promote the quiescent state of NSCs, whereas oscillatory Hes1 expression and the resultant oscillatory Ascl1 expression regulate their active state. Furthermore, in other developmental contexts, high, continuous Hes1 expression induces astrocyte differentiation or the formation of boundaries, which function as signaling centers. Thus, the expression dynamics of Hes1 are a key regulatory mechanism generating and maintaining various cell types in the nervous system.



中文翻译:

基因表达动力学在神经干细胞调控中的意义

神经干细胞(NSC)在胚胎脑中活跃增殖并生成神经元和神经胶质细胞(活动状态),而在成年脑中它们大多处于休眠状态(静止状态)。在活跃和静止的NSC之间,Hes1的表达动力学是不同的。在活跃的NSC中,Hes1的表达振荡并周期性地抑制诸如Ascl1的前代基因的表达,从而驱动其振荡。相比之下,在静止的NSC中,Hes1振荡即使在低谷期(因此是连续的)也保持较高水平的表达,从而连续抑制前神经基因的表达。高水平的Hes1表达和对Ascl1的抑制作用促进NSCs的静态,而振荡的Hes1表达和由此产生的振荡的Ascl1表达调节其活跃状态。此外,在其他发育环境中,高水平,连续的Hes1表达诱导星形胶质细胞分化或边界的形成,其起信号中心的作用。因此,Hes1的表达动力学是在神经系统中产生和维持各种细胞类型的关键调控机制。

更新日期:2020-10-28
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