Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors

Abstract-Text (inkl. Referenzen)

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 recapitulating neural tube development and hypaxial myogenesis. Comparative analyses to in vivo states confirm a pool of hypaxial migrating myogenic progenitors that in a niche dependent manner change their axial/anatomical embryonic developmental program to a fetal myogenic, thereby enabling them to resist specification in a cell autonomous manner, maturate and establish the developmental pool of adult muscle stem cells. Our approach, further validated with patient and CRISPR/Cas9 genome-edited Limb-girdle muscular dystrophy (LGMDR1 ), provides a novel robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis in development and disease.