Institut Mondor de Recherche Biomédicale, INSERM U955-E10, Créteil, France.
Université Paris Est, Faculté de Medecine, Créteil, France.
Elife. 2018 Jun 8;7:e26039. doi: 10.7554/eLife.26039.
Muscle satellite cells are the primary source of stem cells for postnatal skeletal muscle growth and regeneration. Understanding genetic control of satellite cell formation, maintenance, and acquisition of their stem cell properties is on-going, and we have identified SOXF (SOX7, SOX17, SOX18) transcriptional factors as being induced during satellite cell specification. We demonstrate that SOXF factors regulate satellite cell quiescence, self-renewal and differentiation. Moreover, ablation of in the muscle lineage impairs postnatal muscle growth and regeneration. We further determine that activities of SOX7, SOX17 and SOX18 overlap during muscle regeneration, with SOXF transcriptional activity requisite. Finally, we show that SOXF factors also control satellite cell expansion and renewal by directly inhibiting the output of β-catenin activity, including inhibition of and . Together, our findings identify a key regulatory function of SoxF genes in muscle stem cells via direct transcriptional control and interaction with canonical Wnt/β-catenin signaling.
肌卫星细胞是出生后骨骼肌生长和再生的干细胞的主要来源。了解卫星细胞形成、维持和获得其干细胞特性的遗传控制是正在进行的,我们已经确定 SOXF(SOX7、SOX17、SOX18)转录因子在卫星细胞特化过程中被诱导。我们证明 SOXF 因子调节卫星细胞静止、自我更新和分化。此外,在肌肉谱系中缺失 会损害出生后肌肉的生长和再生。我们进一步确定,SOX7、SOX17 和 SOX18 的活性在肌肉再生过程中重叠,SOXF 转录活性是必需的。最后,我们表明 SOXF 因子还通过直接抑制β-连环蛋白活性的输出,包括抑制 和 ,来控制卫星细胞的扩增和更新。总之,我们的研究结果通过直接转录控制和与经典 Wnt/β-连环蛋白信号通路的相互作用,确定了 SoxF 基因在肌肉干细胞中的关键调节功能。