SOXF factors regulate murine satellite cell self-renewal and function through inhibition of β-catenin activity.
SOXF factors regulate murine satellite cell self-renewal and function through inhibition of β-catenin activity.
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DOI：
10.7554/elife.26039
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发表时间：
2018-06-08
期刊：
影响因子：
7.7
通讯作者：
Relaix F
中科院分区：
文献类型：
--
作者：
Alonso-Martin S;Auradé F;Mademtzoglou D;Rochat A;Zammit PS;Relaix F
肌卫星细胞是骨骼肌生长和再生干细胞的主要来源。了解卫星细胞的形成，维护和获取其干细胞特性的遗传控制正在进行中，我们已经确定SOXF（SOX 7，SOX 17，SOX 18）转录因子在卫星细胞特化过程中被诱导。我们证明，SOXF因子调节卫星细胞的静止，自我更新和分化。此外，肌肉谱系中Sox 17的消融损害了出生后肌肉的生长和再生。我们进一步确定了SOX 7，SOX 17和SOX 18的活性在肌肉再生过程中重叠，SOXF转录活性是必需的。最后，我们发现SOXF因子还通过直接抑制β-catenin活性的输出来控制卫星细胞的扩增和更新，包括抑制Ccnd 1和Axin 2。总之，我们的研究结果确定了SoxF基因在肌肉干细胞中通过直接转录控制和与经典Wnt/β-catenin信号转导相互作用的关键调控功能。
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 Sox17 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 Ccnd1 and Axin2. 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.