Fumoto Yoshizuki, Takada Shingo, Onodera Yasuhito, Hatakeyama Shigetsugu, Oikawa Tsukasa
Department of Molecular Biology, Graduate School of Medicine, Hokkaido University, Japan.
Department of Sports Education, Faculty of Lifelong Sport, Hokusho University, Japan.
Biochem Biophys Res Commun. 2024 Dec 31;741:151091. doi: 10.1016/j.bbrc.2024.151091. Epub 2024 Nov 28.
Myogenic differentiation plays a fundamental role in myogenesis during development and in muscle regeneration. Sequential expression of myogenic regulatory factors (MRFs) including myogenin in the progenitor cells triggers the expression of effector proteins such as myosin heavy chain (MHC), leading to the terminal muscle differentiation. Although we have a snapshot-like understanding of molecules at each stage of the differentiation, how these molecules are interrelated in the continuum of myogenic differentiation remains poorly understood. In this study, we analyzed the dynamics of the minimal Myogenin promoter activity in live myoblasts. With the development of a new co-expression analysis method, we were able to reveal in detail the relationship between this Myogenin promoter activity and the expression of endogenous myogenin or MHC, as differentiation markers. Consequently, we found that our visualization system of myogenic differentiation is suitable for monitoring the transition from myoblasts to myotubes, in which the Myogenin promoter activity quantitatively represents the degree of myogenic differentiation. Thus, this system allows simultaneous observation of the degree of myoblast differentiation in relation to other molecules, which would contribute to deepening our understanding of myogenic differentiation as a continuous process.
生肌分化在发育过程中的肌生成以及肌肉再生中起着至关重要的作用。祖细胞中包括肌细胞生成素在内的生肌调节因子（MRFs）的顺序表达触发了诸如肌球蛋白重链（MHC）等效应蛋白的表达，从而导致终末肌肉分化。尽管我们对分化各阶段的分子有了类似快照的了解，但这些分子在生肌分化连续过程中是如何相互关联的仍知之甚少。在本研究中，我们分析了活成肌细胞中最小肌细胞生成素启动子活性的动态变化。随着一种新的共表达分析方法的发展，我们能够详细揭示这种肌细胞生成素启动子活性与作为分化标志物的内源性肌细胞生成素或MHC表达之间的关系。因此，我们发现我们的生肌分化可视化系统适用于监测从成肌细胞到肌管的转变，其中肌细胞生成素启动子活性定量地代表了生肌分化的程度。因此，该系统允许同时观察成肌细胞分化程度与其他分子的关系，这将有助于深化我们对生肌分化作为一个连续过程的理解。
