title: Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro.
abstract: Progress toward finding a cure for muscle diseases has been slow because of the absence of relevant cellular models and the lack of a reliable source of muscle progenitors for biomedical investigation. Here we report an optimized serum-free differentiation protocol to efficiently produce striated, millimeter-long muscle fibers together with satellite-like cells from human pluripotent stem cells (hPSCs) in vitro. By mimicking key signaling events leading to muscle formation in the embryo, in particular the dual modulation of Wnt and bone morphogenetic protein (BMP) pathway signaling, this directed differentiation protocol avoids the requirement for genetic modifications or cell sorting. Robust myogenesis can be achieved in vitro within 1 month by personnel experienced in hPSC culture. The differentiating culture can be subcultured to produce large amounts of myogenic progenitors amenable to numerous downstream applications. Beyond the study of myogenesis, this differentiation method offers an attractive platform for the development of relevant in vitro models of muscle dystrophies and drug screening strategies, as well as providing a source of cells for tissue engineering and cell therapy approaches.
authors: Institut de Génétique et de Biologie Moléculaireet Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden, France.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Boston, Massachusetts, USA.
authors: Jérome
authors: J
authors: Chal
authors: Institut de Génétique et de Biologie Moléculaireet Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden, France.
authors: Ziad
authors: Z
authors: Al Tanoury
authors: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Boston, Massachusetts, USA.
authors: Marie
authors: M
authors: Hestin
authors: Institut de Génétique et de Biologie Moléculaireet Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden, France.
authors: Bénédicte
authors: B
authors: Gobert
authors: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Boston, Massachusetts, USA.
authors: Suvi
authors: S
authors: Aivio
authors: Anagenesis Biotechnologies, Parc d'innovation, Illkirch-Graffenstaden, France.
authors: Aurore
authors: A
authors: Hick
authors: Institut de Génétique et de Biologie Moléculaireet Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden, France.
authors: Thomas
authors: T
authors: Cherrier
authors: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
authors: Alexander P
authors: AP
authors: Nesmith
authors: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.
authors: Kevin K
authors: KK
authors: Parker
authors: Institut de Génétique et de Biologie Moléculaireet Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch-Graffenstaden, France.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.|Harvard Stem Cell Institute, Boston, Massachusetts, USA.
authors: Olivier
authors: O
authors: Pourquié
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*