During muscle regeneration, extracellular signal-regulated kinase (ERK) promotes both proliferation and migration. However, the relationship between proliferation and migration is poorly understood in this context. To elucidate this complex relationship on a physiological level, we established an intravital imaging system for measuring ERK activity, migration speed, and cell-cycle phases in mouse muscle satellite cells. We found that in vivo, ERK was maximally activated in satellite cells two days after injury, and this is then followed by increases in cell number and motility. With limited effects of immediate ERK activity on migration, we hypothesized that ERK increases migration speed in the later phase by promoting cell-cycle progression. Our cell-cycle analysis further revealed that in satellite cells, ERK activity is critical for the G1/S transition, and cells migrate more rapidly in the S/G2 phase three days after injury. Finally, migration speed of satellite cells was suppressed after CDK1/2, but not CDK1, inhibitor treatment, demonstrating a critical role of CDK2 in satellite cell migration. Overall, our study demonstrates that in satellite cells, the ERK-CDK2 axis not only promotes the G1/S transition, but also migration speed, which may provide a novel mechanism for efficient muscle regeneration.

中文翻译：

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活体成像显示肌肉再生过程中依赖细胞周期的卫星细胞迁移。

在肌肉再生过程中，细胞外信号调节激酶（ERK）促进增殖和迁移。但是，在这种情况下，人们对扩散与迁移之间的关系知之甚少。为了在生理学水平上阐明这种复杂的关系，我们建立了一种活体内成像系统，用于测量小鼠肌肉卫星细胞中的ERK活性，迁移速度和细胞周期阶段。我们发现在体内，损伤后两天，ERK在卫星细胞中被最大程度激活，然后细胞数量和运动性增加。由于即时ERK活性对迁移的影响有限，我们假设ERK通过促进细胞周期进程在后期增加迁移速度。我们的细胞周期分析进一步表明，在卫星细胞中，ERK活性对于G1 / S过渡至关重要，在损伤后三天，细胞在S / G2期迁移更快。最后，在CDK1 / 2抑制剂处理后抑制了卫星细胞的迁移速度，但没有抑制CDK1抑制剂的处理，证明了CDK2在卫星细胞迁移中的关键作用。总体而言，我们的研究表明，在卫星细胞中，ERK-CDK2轴不仅促进G1 / S过渡，而且还促进迁移速度，这可能为有效的肌肉再生提供了新的机制。