Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis.
Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis.
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肌原素是成人肌纤维生长和肌肉干细胞稳态的重要调节因子。
DOI：
10.7554/elife.60445
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发表时间：
2020-10-01
期刊：
影响因子：
7.7
通讯作者：
Hughes SM
中科院分区：
文献类型：
--
作者：
Ganassi M;Badodi S;Wanders K;Zammit PS;Hughes SM
骨骼肌纤维的生长和维持依赖于驻留肌肉干细胞（MuSC）的协调激活和恢复静止。转录因子肌细胞生成素（Myog）在发育过程中调节肌细胞融合，但其在成人肌发生中的作用仍不清楚。与小鼠相比，myog-/-斑马鱼是可行的，但具有营养不良的肌肉。通过分离具有相关MuSC的成人肌纤维，我们发现肌细胞-/-肌纤维具有严重减少的核数目，但增加了肌细胞结构域大小。融合基因的表达减少，Pax7上调，MuSC的数量增加五倍，并且在整个肌纤维长度上错误定位，而不是像野生型那样定位在肌纤维末端。Myog的缺失会失调mTORC 1信号传导，导致MuSC处于“警报”状态，这些MuSC在体外表现出早熟激活和更快的细胞周期进入，同时伴有myod上调。因此，除了控制肌细胞融合外，Myog还影响MuSC：生态位关系，表明对整个生命过程中的肌肉稳态有多层次的贡献。
Growth and maintenance of skeletal muscle fibres depend on coordinated activation and return to quiescence of resident muscle stem cells (MuSCs). The transcription factor Myogenin (Myog) regulates myocyte fusion during development, but its role in adult myogenesis remains unclear. In contrast to mice, myog-/-zebrafish are viable, but have hypotrophic muscles. By isolating adult myofibres with associated MuSCs, we found that myog-/- myofibres have severely reduced nuclear number, but increased myonuclear domain size. Expression of fusogenic genes is decreased, Pax7 upregulated, MuSCs are fivefold more numerous and mis-positioned throughout the length of myog-/-myofibres instead of localising at myofibre ends as in wild-type. Loss of Myog dysregulates mTORC1 signalling, resulting in an ‘alerted’ state of MuSCs, which display precocious activation and faster cell cycle entry ex vivo, concomitant with myod upregulation. Thus, beyond controlling myocyte fusion, Myog influences the MuSC:niche relationship, demonstrating a multi-level contribution to muscle homeostasis throughout life.