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

Abstract : Key cell types including skeletal muscle have proven difficult to differentiate in vitro from pluripotent cells. During embryonic development, skeletal muscles arise from somites, which derive from the presomitic mesoderm (PSM). Based on our understanding of PSM development, we established serum-free conditions allowing efficient differentiation of monolayer cultures of mouse embryonic stem (ES) cells into PSM-like cells without introduction of exogenous genetic material or cell sorting. We show that primary and secondary skeletal myogenesis can be recapitulated in vitro from these PSM-like cells. Our strategy allowed for the production of striated contractile fibers from mouse and human pluripotent cells in vitro with an efficiency comparing with current cardiomyocytes differentiation protocols. We also differentiated ES cells into Pax7-positive cells with satellite cell characteristics, including the ability to generate dystrophin-positive fibers when grafted into muscles from dystrophin-deficient mdx mice. We show that differentiated ES cells derived from mdx mice exhibit a striking branched phenotype resembling that described in vivo, thus providing an attractive model to study the origin of the pathological defects associated with Duchenne Muscular Dystrophy.
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Jérome Chal, Masayuki Oginuma, Ziad Al Tanoury, Bénédicte Gobert, Olga Sumara, et al.. Differentiation of pluripotent stem cells to muscle fiber to model Duchenne muscular dystrophy. Nature Biotechnology, Nature Publishing Group, 2015, 33 (9), pp.962-9. 〈10.1038/nbt.3297〉. 〈inserm-01484878〉

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