Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Muscle Biology Laboratory, Research Team for Aging Science, Tokyo Metropolitan Institute for Geriatric and Gerontology (TMIG), Tokyo, Japan.
Sci Rep. 2024 Sep 5;14(1):20699. doi: 10.1038/s41598-024-71739-y.
Insulin-like growth factor (IGF)-I mediates long-term activities that determine cell fate, including cell proliferation and differentiation. This study aimed to characterize the mechanisms by which IGF-I determines cell fate from the aspect of IGF-I signaling dynamics. In L6 myoblasts, myogenic differentiation proceeded under low IGF-I levels, whereas proliferation was enhanced under high levels. Mathematical and experimental analyses revealed that IGF-I signaling oscillated at low IGF-I levels but remained constant at high levels, suggesting that differences in IGF-I signaling dynamics determine cell fate. We previously reported that differential insulin receptor substrate (IRS)-1 levels generate a driving force for cell competition. Computational simulations and immunofluorescence analyses revealed that asynchronous IRS-1 protein oscillations were synchronized during myogenic processes through cell competition. Disturbances of cell competition impaired signaling synchronization and cell fusion, indicating that synchronization of IGF-I signaling oscillation is critical for myoblast cell fusion to form multinucleate myotubes.
胰岛素样生长因子-I（IGF-I）介导决定细胞命运的长期活动，包括细胞增殖和分化。本研究旨在从 IGF-I 信号转导动力学的角度来描述 IGF-I 决定细胞命运的机制。在 L6 成肌细胞中，低 IGF-I 水平下进行成肌分化，而高 IGF-I 水平下促进增殖。数学和实验分析表明，IGF-I 信号在低 IGF-I 水平下呈振荡状态，而在高 IGF-I 水平下保持稳定，这表明 IGF-I 信号转导动力学的差异决定了细胞命运。我们之前曾报道过，胰岛素受体底物（IRS）-1 水平的差异产生了细胞竞争的驱动力。计算模拟和免疫荧光分析表明，在成肌过程中，通过细胞竞争，异步 IRS-1 蛋白振荡被同步。细胞竞争的干扰破坏了信号同步和细胞融合，表明 IGF-I 信号振荡的同步对于成肌细胞融合形成多核肌管至关重要。
