Cell 2013-11-01

A zebrafish embryo culture system defines factors that promote vertebrate myogenesis across species.

Cong Xu, Mohammadsharif Tabebordbar, Salvatore Iovino, Christie Ciarlo, Jingxia Liu, Alessandra Castiglioni, Emily Price, Min Liu, ElisabethR Barton, CRonald Kahn, AmyJ Wagers, LeonardI Zon

Index: Cell 155(4) , 909-21, (2013)

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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 GSK3_ 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 GSK3_ 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.