Epigenetic reprogramming of human embryonic stem cells into skeletal muscle cells and generation of contractile myospheres

Cell Rep. 2013 Mar 28;3(3):661-70. doi: 10.1016/j.celrep.2013.02.012. Epub 2013 Mar 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Cell Lineage
  • Cellular Reprogramming*
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism*
  • Epigenesis, Genetic*
  • Humans
  • Mesoderm / cytology
  • Muscle Contraction
  • Muscle Development / genetics
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / physiology
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Chromosomal Proteins, Non-Histone
  • MyoD Protein
  • MyoD1 myogenic differentiation protein
  • SMARCD3 protein, human
  • Transcription Factors