Chen Wan-Jing, Lin I-Hsuan, Lee Chien-Wei, Yoshioka Kiyoshi, Ono Yusuke, Yan Yu-Ting, Yen Yun, Chen Yi-Fan
The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, 11529, Taiwan.
TMU Research Center of Cancer Translational Medicine, Taipei Medical University, 11031, Taipei, Taiwan.
NPJ Regen Med. 2022 Jul 29;7(1):37. doi: 10.1038/s41536-022-00231-w.
The balance among quiescence, differentiation, and self-renewal of skeletal muscle stem cells (MuSCs) is tightly regulated by their intrinsic and extrinsic properties from the niche. How the niche controls MuSC fate remains unclear. Ribonucleotide reductase M2B (Rrm2b) modulates MuSC quiescence/differentiation in muscle in response to injury. Rrm2b knockout in myofibers, but not in MuSCs, led to weakness of muscles, such as a loss of muscle mass and strength. After muscle injury, damaged myofibers were more efficiently repaired in the Rrm2b myofiber-specific knockout mice than the control mice, but these myofibers were thinner and showed weak functioning. Rrm2b-deleted myofibers released several myokines, which trigger MuSCs to differentiate but not re-enter the quiescent stage to replenish the stem cell pool. Overall, Rrm2b in the myofibers plays a critical role in modulating the MuSC fate by modifying the microenvironment, and it may lead to a possible strategy to treat muscle disorders.
骨骼肌干细胞（MuSCs）的静止、分化和自我更新之间的平衡受到其内在特性以及来自微环境的外在特性的严格调控。微环境如何控制MuSC的命运仍不清楚。核糖核苷酸还原酶M2B（Rrm2b）响应损伤调节肌肉中MuSC的静止/分化。在肌纤维而非MuSCs中敲除Rrm2b会导致肌肉无力，如肌肉质量和力量的丧失。肌肉损伤后，Rrm2b肌纤维特异性敲除小鼠中受损的肌纤维比对照小鼠得到更有效的修复，但这些肌纤维更细且功能较弱。缺失Rrm2b的肌纤维释放出几种肌动蛋白，它们促使MuSCs分化，但不会重新进入静止阶段以补充干细胞池。总体而言，肌纤维中的Rrm2b通过改变微环境在调节MuSC命运中起关键作用，并且这可能会带来一种治疗肌肉疾病的潜在策略。
