Ruhr University Bochum, Medical Faculty, Institute of Anatomy, Department of Anatomy and Molecular Embryology, Bochum, Germany.
Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Münster, Germany.
Elife. 2023 Nov 14;12:RP87081. doi: 10.7554/eLife.87081.
In vitro culture systems that structurally model human myogenesis and promote PAX7 myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (//) and dormant (//) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.
尚未建立结构上模拟人类成肌发生并促进 PAX7 成肌祖细胞成熟的体外培养系统。在这里，我们报告说，可以从诱导多能干细胞系分化出人骨骼肌类器官，使其包含轴旁中胚层和神经中胚层祖细胞，并发育成重新组装神经板边界和真皮肌节的有组织结构。培养条件会引发神经谱系停滞，并促进胎儿下轴成肌发生向肢体轴向解剖特征，产生可持续的未分化 PAX7 成肌祖细胞和纤维脂肪祖细胞（PDGFRa+）群体，相当于人类妊娠第二个三个月的水平。与人类胎儿和成人成肌祖细胞/卫星细胞的单细胞比较揭示了处于激活（//）和休眠（//）状态的非分裂成肌祖细胞的独特分子特征。我们的方法提供了一个强大的 3D 体外发育系统，可用于研究肌肉组织形态发生和动态平衡。
