Experimental cell therapies for skeletal muscle conditions have shown little success, primarily because they use committed myogenic progenitors rather than true muscle stem cells, known as satellite cells. Here we present a method to generate in vitro-derived satellite cells (idSCs) from skeletal muscle tissue. When transplanted in small numbers into mouse muscle, mouse idSCs fuse into myofibers, repopulate the satellite cell niche, self-renew, support multiple rounds of muscle regeneration and improve force production on par with freshly isolated satellite cells in damaged skeletal muscle. We compared the epigenomic and transcriptional signatures between idSCs, myoblasts and satellite cells and used these signatures to identify core signaling pathways and genes that confer idSC functionality. Finally, from human muscle biopsies, we successfully generated satellite cell-like cells in vitro. After further development, idSCs may provide a scalable source of cells for the treatment of genetic muscle disorders, trauma-induced muscle damage and age-related muscle weakness.

针对骨骼肌疾病的实验性细胞疗法收效甚微，主要是因为它们使用的是定向生肌祖细胞，而不是真正的肌肉干细胞（即卫星细胞）。在这里，我们提出了一种从骨骼肌组织产生体外衍生卫星细胞（idSC）的方法。当少量移植到小鼠肌肉中时，小鼠 idSC 会融合到肌纤维中，重新填充卫星细胞生态位，自我更新，支持多轮肌肉再生，并提高与受损骨骼肌中新鲜分离的卫星细胞相同的力量产生。我们比较了 idSC、成肌细胞和卫星细胞之间的表观基因组和转录特征，并使用这些特征来识别核心信号通路和赋予 idSC 功能的基因。最后，我们从人体肌肉活检中成功地在体外生成了卫星细胞样细胞。经过进一步开发，idSC 可能为治疗遗传性肌肉疾病、创伤引起的肌肉损伤和年龄相关的肌肉无力提供可扩展的细胞来源。