Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

Sonia Albini, Paula Coutinho, Barbora Malecova, Lorenzo Giordani, Alex Savchenko, Sonia Vanina Forcales, Pier Lorenzo Puri

Research output: Contribution to journalArticle

Abstract

Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs) and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB), but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3) confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for " disease in a dish" models of muscular physiology and dysfunction.

Original languageEnglish
Pages (from-to)661-670
Number of pages10
JournalCell Reports
Volume3
Issue number3
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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