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.
Commun Biol. 2022 Nov 9;5(1):1201. doi: 10.1038/s42003-022-04176-0.
Muscle stem cells (MuSCs) are essential for skeletal muscle development and regeneration, ensuring muscle integrity and normal function. The myogenic proliferation and differentiation of MuSCs are orchestrated by a cascade of transcription factors. In this study, we elucidate the specific role of transcription factor 12 (Tcf12) in muscle development and regeneration based on loss-of-function studies. Muscle-specific deletion of Tcf12 cause muscle weight loss owing to the reduction of myofiber size during development. Inducible deletion of Tcf12 specifically in adult MuSCs delayed muscle regeneration. The examination of MuSCs reveal that Tcf12 deletion resulted in cell-autonomous defects during myogenesis and Tcf12 is necessary for proper myogenic gene expression. Mechanistically, TCF12 and MYOD work together to stabilise chromatin conformation and sustain muscle cell fate commitment-related gene and chromatin architectural factor expressions. Altogether, our findings identify Tcf12 as a crucial regulator of MuSCs chromatin remodelling that regulates muscle cell determination and participates in skeletal muscle development and regeneration.
肌肉干细胞（MuSCs）对于骨骼肌的发育和再生至关重要，确保了肌肉的完整性和正常功能。MuSCs 的肌生成增殖和分化是由一系列转录因子级联协调的。在这项研究中，我们基于功能丧失研究阐明了转录因子 12（Tcf12）在肌肉发育和再生中的特定作用。肌肉特异性敲除 Tcf12 会导致肌肉重量减轻，这是由于发育过程中肌纤维大小的减少。在成年 MuSCs 中诱导性敲除 Tcf12 会延迟肌肉再生。对 MuSCs 的检查表明，Tcf12 缺失导致成肌过程中的细胞自主缺陷，并且 Tcf12 对于适当的肌生成基因表达是必需的。在机制上，TCF12 和 MYOD 共同作用以稳定染色质构象，并维持肌肉细胞命运决定相关基因和染色质结构因子的表达。总之，我们的发现确定了 Tcf12 是 MuSCs 染色质重塑的关键调节剂，它调节肌肉细胞的决定，并参与骨骼肌肉的发育和再生。
