关键词: Ascl1 Hes1 Neural stem cells Neuronal differentiation Oligo2 Physiological electric fields

Mesh : Animals Mice Basic Helix-Loop-Helix Transcription Factors / genetics Brain Cell Differentiation Electric Stimulation RNA, Messenger / genetics Transcription Factor HES-1 / genetics Oligodendrocyte Transcription Factor 2 / genetics

来  源:   DOI:10.1007/s11033-023-09118-5

Abstract:
BACKGROUND: Recent studies have shown that the expression of bHLH transcription factors Hes1, Ascl1, and Oligo2 has an oscillating balance in neural stem cells (NSCs) to maintain their self-proliferation and multi-directional differentiation potential. This balance can be disrupted by exogenous stimulation. Our previous work has identified that electrical stimulation could induce neuronal differentiation of mouse NSCs.
METHODS: To further evaluate if physiological electric fields (EFs)-induced neuronal differentiation is related to the expression patterns of bHLH transcription factors Hes1, Ascl1, and Oligo2, mouse embryonic brain NSCs were used to investigate the expression changes of Ascl1, Hes1 and Oligo2 in mRNA and protein levels during EF-induced neuronal differentiation.
RESULTS: Our results showed that NSCs expressed high level of Hes1, while expression of Ascl1 and Oligo2 stayed at very low levels. When NSCs exited proliferation, the expression of Hes1 in differentiated cells began to decrease and oscillated at the low expression level. Oligo2 showed irregular changes in low expression level. EF-stimulation significantly increased the expression of Ascl1 at mRNA and protein levels accompanied by an increased percentage of neuronal differentiation. What\'s more, over-expression of Hes1 inhibited the neuronal differentiation induced by EFs.
CONCLUSIONS: EF-stimulation directed neuronal differentiation of NSCs by promoting the continuous accumulation of Ascl1 expression and decreasing the expression of Hes1.
摘要:
背景:最近的研究表明,bHLH转录因子Hes1、Ascl1和Oligo2的表达在神经干细胞(NSC)中具有振荡平衡,维持其自我增殖和多向分化潜能。这种平衡可以被外源刺激破坏。我们先前的工作已经确定电刺激可以诱导小鼠神经干细胞的神经元分化。
方法:为了进一步评估生理电场(EF)诱导的神经元分化是否与bHLH转录因子Hes1、Ascl1、Oligo2的表达模式有关,用小鼠胚胎脑神经干细胞研究EF诱导的神经元分化过程中Ascl1、Hes1、Oligo2在mRNA和蛋白水平上的表达变化。
结果:我们的结果表明,NSCs表达高水平的Hes1,而Ascl1和Oligo2的表达保持在非常低的水平。当NSC退出增殖时,Hes1在分化细胞中的表达开始降低并在低表达水平振荡。Oligo2在低表达水平上表现出不规则的变化。EF刺激显着增加了mRNA和蛋白质水平的Ascl1表达,并伴随着神经元分化百分比的增加。更重要的是,Hes1的过表达抑制了EF诱导的神经元分化。
结论:EF通过促进Ascl1表达的持续积累和降低Hes1的表达来刺激神经干细胞的神经元分化。
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