State Key Laboratory of Molecular Neuroscience, Division of Life Science, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China.
Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen 518055, China.
Int J Mol Sci. 2022 Feb 3;23(3):1748. doi: 10.3390/ijms23031748.
Skeletal muscle harbors a pool of stem cells called muscle satellite cells (MuSCs) that are mainly responsible for its robust regenerative capacities. Adult satellite cells are mitotically quiescent in uninjured muscles under homeostasis, but they exit quiescence upon injury to re-enter the cell cycle to proliferate. While most of the expanded satellites cells differentiate and fuse to form new myofibers, some undergo self-renewal to replenish the stem cell pool. Specifically, quiescence exit describes the initial transition of MuSCs from quiescence to the first cell cycle, which takes much longer than the time required for subsequent cell cycles and involves drastic changes in cell size, epigenetic and transcriptomic profiles, and metabolic status. It is, therefore, an essential period indispensable for the success of muscle regeneration. Diverse mechanisms exist in MuSCs to regulate quiescence exit. In this review, we summarize key events that occur during quiescence exit in MuSCs and discuss the molecular regulation of this process with an emphasis on multiple levels of intrinsic regulatory mechanisms. A comprehensive understanding of how quiescence exit is regulated will facilitate satellite cell-based muscle regenerative therapies and advance their applications in various disease and aging conditions.
骨骼肌中存在一类被称为肌卫星细胞（MuSCs）的干细胞，其主要负责肌肉强大的再生能力。在正常情况下，未受伤的肌肉中的成年卫星细胞处于有丝分裂静止状态，但在受伤后，它们会退出静止状态，重新进入细胞周期进行增殖。虽然大部分扩增的卫星细胞会分化并融合形成新的肌纤维，但有些细胞会自我更新，以补充干细胞池。具体来说，静止期退出描述了 MuSCs 从静止期到第一个细胞周期的初始过渡，这一过程所需的时间比后续细胞周期长得多，并且涉及细胞大小、表观遗传和转录组特征以及代谢状态的剧烈变化。因此，这是肌肉再生成功所必需的关键时期。MuSCs 中存在多种调节静止期退出的机制。在这篇综述中，我们总结了 MuSCs 中静止期退出过程中发生的关键事件，并讨论了这一过程的分子调控，重点是多个内在调控机制的水平。全面了解静止期退出是如何被调控的，将有助于基于卫星细胞的肌肉再生疗法，并推进其在各种疾病和衰老条件下的应用。
