Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells

Cardiovasc Res. 2014 Nov 1;104(2):258-69. doi: 10.1093/cvr/cvu205. Epub 2014 Sep 10.


Aims: Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.

Methods and results: To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for 'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.

Conclusion: Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.

Keywords: Cardiomyocyte; Heart; Hypertrophic cardiomyopathy; Induced pluripotent stem cells.

Publication types

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

MeSH terms

  • Action Potentials
  • Adult
  • Animals
  • Calcium Signaling / genetics
  • Cardiac Myosins / genetics
  • Cardiomyopathy, Hypertrophic, Familial / genetics*
  • Cardiomyopathy, Hypertrophic, Familial / metabolism
  • Cardiomyopathy, Hypertrophic, Familial / pathology
  • Case-Control Studies
  • Cell Proliferation / genetics
  • Cell Separation / methods
  • Cells, Cultured
  • Cellular Reprogramming
  • Cellular Reprogramming Techniques
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Induced Pluripotent Stem Cells / ultrastructure
  • Mice, Inbred NOD
  • Mice, SCID
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / ultrastructure
  • Myosin Heavy Chains / genetics
  • Phenotype
  • Sarcomeres / metabolism
  • Sarcomeres / ultrastructure
  • Transcriptome


  • MYH7 protein, human
  • Cardiac Myosins
  • Myosin Heavy Chains