Distinct embryonic and adult fates of multipotent myogenic progenitors isolated from skeletal muscle and bone marrow

Identification of multipotent progenitors has been difficult due to their rarity in adults. Here, we report a novel type of neuroepithelial myogenic progenitor that can be isolated from adult murine skeletal muscle. In culture, these progenitors generated radial glia-like cells that initiated mosaic myotubes, and subsequently developed into embryonic/fetal-like myoblasts capable of robust myofiber formation. These cells could also differentiate into neuronal lineage. By contrast, progenitors from bone marrow produced progenies more uniformly of an adult myoblast lineage. When grafted into dystrophic muscles of mdx mice, the muscle- and marrow-derived cells restored dystrophin expression; however, fetal-like myogenesis towards a defective adult fate was demonstrated in the muscle-derived cells. This impaired regenerative capacity resembled Duchenne muscular dystrophy patients, suggesting a potential connection between the neuroepithelial myogenic progenitor and the etiology of this myopathy. The distinct fates of the two types of progenitors imply their different roles in muscle regeneration and pathogenesis.