Department of Human Genetics, McGill University, Montréal, QC, Canada.
Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada.
EMBO Rep. 2020 Dec 3;21(12):e49499. doi: 10.15252/embr.201949499. Epub 2020 Oct 13.
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.
肌肉干细胞（MuSCs）的功能和维持受到其龛位环境中起源的信号的严格调控。骨骼肌纤维是 MuSC 龛位的主要组成部分，与肌肉干细胞直接接触。在这里，我们表明 Myf6 在肌肉干细胞与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 在骨骼肌纤维中转录调控广泛的肌肉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 纯合缺失导致肌肉产生 EGF 的能力显著降低，导致 EGFR 信号通路失调。因此，尽管 Myf6 敲除小鼠出生时具有正常的肌肉干细胞池，但由于自发退出静止状态，它们在出生后生活中经历了干细胞池的逐渐减少。总之，我们的数据揭示了 Myf6 在促进肌肉纤维中关键肌肉因子（如 EGF）表达中的新作用，通过阻止其过早分化来防止肌肉干细胞衰竭。
