Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy.

摘要: Key cell types including skeletal muscle have proven difficult to differentiate in vitro from pluripotent cells. During embryonic development, muscles arise somites, which derive the presomitic mesoderm (PSM). Based on our understanding of PSM we established serum-free conditions allowing efficient differentiation monolayer cultures mouse stem (ES) cells into PSM-like without introduction exogenous genetic material or sorting. We show that primary and secondary myogenesis can be recapitulated in vitro these Our strategy allowed for the production striated contractile fibers human cells in with an efficiency comparing current cardiomyocytes differentiation protocols. also differentiated ES Pax7-positive satellite cell characteristics, ability generate dystrophin-positive fibers when grafted muscles dystrophin-deficient mdx mice. that differentiated derived mice exhibit a striking branched phenotype resembling described vivo, thus providing attractive model to study origin pathological defects associated Duchenne Muscular Dystrophy.