Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Graduate Program in Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Stem Cell Reports. 2017 Oct 10;9(4):1139-1151. doi: 10.1016/j.stemcr.2017.08.014. Epub 2017 Sep 21.
Satellite cells are skeletal-muscle-specific stem cells that are activated by injury to proliferate, differentiate, and fuse to enable repair. SOX7, a member of the SRY-related HMG-box family of transcription factors is expressed in quiescent satellite cells. To elucidate SOX7 function in skeletal muscle, we knocked down Sox7 expression in embryonic stem cells and primary myoblasts and generated a conditional knockout mouse in which Sox7 is excised in PAX3 cells. Loss of Sox7 in embryonic stem cells reduced Pax3 and Pax7 expression. In vivo, conditional knockdown of Sox7 reduced the satellite cell population from birth, reduced myofiber caliber, and impaired regeneration after acute injury. Although Sox7-deficient primary myoblasts differentiated normally, impaired myoblast fusion and increased sensitivity to apoptosis in culture and in vivo were observed. Taken together, these results indicate that SOX7 is dispensable for myogenesis but is necessary to promote satellite cell development and survival.
卫星细胞是骨骼肌特异性干细胞，它们在受到损伤时被激活，通过增殖、分化和融合来进行修复。SOX7 是 SOX 转录因子家族的成员之一，在静止的卫星细胞中表达。为了阐明 SOX7 在骨骼肌中的功能，我们在胚胎干细胞和原代成肌细胞中敲低 Sox7 的表达，并在 PAX3 细胞中敲除 Sox7 生成条件性敲除小鼠。胚胎干细胞中 Sox7 的缺失降低了 Pax3 和 Pax7 的表达。在体内，条件性敲低 Sox7 从出生时就减少了卫星细胞群体，减少了肌纤维口径，并损害了急性损伤后的再生。尽管 Sox7 缺陷型原代成肌细胞正常分化，但在培养中和体内观察到成肌细胞融合受损和凋亡敏感性增加。总之，这些结果表明 SOX7 对于肌发生不是必需的，但对于促进卫星细胞的发育和存活是必需的。
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