title: Myocardin overexpression is sufficient for promoting the development of a mature smooth muscle cell-like phenotype from human embryonic stem cells.
abstract: BACKGROUND
  Myocardin is thought to have a key role in smooth muscle cell (SMC) development by acting on CArG-dependent genes. However, it is unclear whether myocardin-induced SMC maturation and increases in agonist-induced calcium signalling are also associated with increases in the expression of non-CArG-dependent SMC-specific genes. Moreover, it is unknown whether myocardin promotes SMC development from human embryonic stem cells.
  
  
  RESULTS
  Findings The effects of adenoviral-mediated myocardin overexpression on SMC development in human ESC-derived embryoid bodies were investigated using immunofluorescence, flow cytometry and real time RT-PCR. Myocardin overexpression from day 10 to day 28 of embryoid body differentiation increased the number of smooth muscle α-actin(+) and smooth muscle myosin heavy chain(+) SMC-like cells and increased carbachol-induced contractile function. However, myocardin was found to selectively regulate only CArG-dependent SMC-specific genes. Nevertheless, myocardin expression appeared to be sufficient to specify the SMC lineage.
  
  
  CONCLUSIONS
  Myocardin increases the development and maturation of SMC-like cells from human embryonic stem cells despite not activating the full repertoire of SMC genes. These findings have implications for vascular tissue engineering and other applications requiring large numbers of functional SMCs.
authors.affiliation: Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Linda
authors.initials: L
authors.lastname: Raphel
authors.forename: Amarnath
authors.initials: A
authors.lastname: Talasila
authors.forename: Christine
authors.initials: C
authors.lastname: Cheung
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sinha
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000099251:Myocardin
chemical_list: D018995:Myosin Heavy Chains; D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin