title: A zebrafish embryo culture system defines factors that promote vertebrate myogenesis across species.
abstract: Ex vivo expansion of satellite cells and directed differentiation of pluripotent cells to mature skeletal muscle have proved difficult challenges for regenerative biology. Using a zebrafish embryo culture system with reporters of early and late skeletal muscle differentiation, we examined the influence of 2,400 chemicals on myogenesis and identified six that expanded muscle progenitors, including three GSK3β inhibitors, two calpain inhibitors, and one adenylyl cyclase activator, forskolin. Forskolin also enhanced proliferation of mouse satellite cells in culture and maintained their ability to engraft muscle in vivo. A combination of bFGF, forskolin, and the GSK3β inhibitor BIO induced skeletal muscle differentiation in human induced pluripotent stem cells (iPSCs) and produced engraftable myogenic progenitors that contributed to muscle repair in vivo. In summary, these studies reveal functionally conserved pathways regulating myogenesis across species and identify chemical compounds that expand mouse satellite cells and differentiate human iPSCs into engraftable muscle.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.|Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Xu
authors.affiliation: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Mohammadsharif
authors.initials: M
authors.lastname: Tabebordbar
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.|Joslin Diabetes Center, Boston, MA 02115, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Iovino
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.|Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christie
authors.initials: C
authors.lastname: Ciarlo
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.|Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Joslin Diabetes Center, Boston, MA 02115, USA.|Vita-Salute San Raffaele University, Milan, 20132, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Castiglioni
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.|Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Price
authors.affiliation: Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
authors.affiliation: Harvard Medical School, Boston, MA 02115, USA.|Joslin Diabetes Center, Boston, MA 02115, USA.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.affiliation: Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.|Joslin Diabetes Center, Boston, MA 02115, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Wagers
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.|Howard Hughes Medical Institute, Harvard Stem Cell Institute, Boston, MA 02115, USA.|Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology; D009136:Muscular Dystrophies / Q000628:therapy; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D033581:Stem Cell Transplantation; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism
chemical_list: D005576:Colforsin; D000242:Cyclic AMP