Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of the Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
College of Animal Science and Technology, Shandong Agricultural University, Taian, China.
Cell Death Dis. 2022 Sep 29;13(9):838. doi: 10.1038/s41419-022-05284-9.
In adult skeletal muscle, satellite cells are in a quiescent state, which is essential for the future activation of muscle homeostasis and regeneration. Multiple studies have investigated satellite cell proliferation and differentiation, but the molecular mechanisms that safeguard the quiescence of satellite cells remain largely unknown. In this study, we purposely activated dormant satellite cells by using various stimuli and captured the in vivo-preserved features from quiescence to activation transitions. We found that retinoic acid signaling was required for quiescence maintenance. Mechanistically, retinoic acid receptor gamma (RARγ) binds to and stimulates genes responsible for Akt dephosphorylation and subsequently inhibits overall protein translation initiation in satellite cells. Furthermore, the alleviation of retinoic acid signaling released the satellite cells from quiescence, but this restraint was lost in aged cells. Retinoic acid also preserves the quiescent state during satellite cell isolation, overcoming the cellular stress caused by the isolation process. We conclude that active retinoic acid signaling contributes to the maintenance of the quiescent state of satellite cells through regulation of the protein translation initiation process.
在成人骨骼肌中，卫星细胞处于静止状态，这对于未来肌肉稳态和再生的激活至关重要。多项研究已经研究了卫星细胞的增殖和分化，但维持卫星细胞静止的分子机制在很大程度上仍然未知。在这项研究中，我们通过使用各种刺激物故意激活休眠的卫星细胞，并从静止到激活的转变过程中捕获体内保存的特征。我们发现视黄酸信号对于维持静止状态是必需的。从机制上讲，视黄酸受体γ（RARγ）与负责 Akt 去磷酸化的基因结合并刺激它们，从而抑制卫星细胞中整体蛋白质翻译起始。此外，视黄酸信号的缓解使卫星细胞从静止状态中释放出来，但在衰老细胞中这种限制消失了。视黄酸还可以在卫星细胞分离过程中保持静止状态，克服了分离过程中引起的细胞应激。我们得出结论，活跃的视黄酸信号通过调节蛋白质翻译起始过程有助于维持卫星细胞的静止状态。
