The function and maintenance of muscle stem cells (MuSCs) are tightly regulated by signals originating from their niche environment. Skeletal myofibers are a principle component of the MuSC niche and are in direct contact with the muscle stem cells. Here, we show that Myf6 establishes a ligand/receptor interaction between muscle stem cells and their associated muscle fibers. Our data show that Myf6 transcriptionally regulates a broad spectrum of myokines and muscle‐secreted proteins in skeletal myofibers, including EGF. EGFR signaling blocks p38 MAP kinase‐induced differentiation of muscle stem cells. Homozygous deletion of Myf6 causes a significant reduction in the ability of muscle to produce EGF, leading to a deregulation in EGFR signaling. Consequently, although Myf6‐knockout mice are born with a normal muscle stem cell compartment, they undergo a progressive reduction in their stem cell pool during postnatal life due to spontaneous exit from quiescence. Taken together, our data uncover a novel role for Myf6 in promoting the expression of key myokines, such as EGF, in the muscle fiber which prevents muscle stem cell exhaustion by blocking their premature differentiation.

中文翻译：

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Myf6/MRF4 是维持肌肉干细胞池所需的生肌生态位调节剂

肌肉干细胞 (MuSC) 的功能和维持受到来自其利基环境的信号的严格调控。骨骼肌纤维是 MuSC 生态位的主要组成部分，与肌肉干细胞直接接触。在这里，我们表明 Myf6 在肌肉干细胞及其相关的肌肉纤维之间建立了配体/受体相互作用。我们的数据表明，Myf6 转录调节骨骼肌纤维中广泛的肌因子和肌肉分泌蛋白，包括 EGF。EGFR 信号通路阻断 p38 MAP 激酶诱导的肌肉干细胞分化。Myf6 的纯合缺失导致肌肉产生 EGF 的能力显着降低，从而导致 EGFR 信号传导的失调。因此，尽管 Myf6 基因敲除小鼠出生时具有正常的肌肉干细胞区室，由于自发地从静止状态中退出，他们在出生后的生命中干细胞库逐渐减少。总之，我们的数据揭示了 Myf6 在促进肌纤维中关键肌细胞因子（如 EGF）表达方面的新作用，通过阻止其过早分化来防止肌肉干细胞衰竭。