4.8 Article

Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature

Journal

CELL RESEARCH
Volume 22, Issue 1, Pages 142-154

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2011.171

Keywords

induced pluripotent stem cells; ventricular cardiomyocyte; regenerative medicine; epigenetic memory

Categories

Funding

  1. Massachusetts General Hospital Executive Committee
  2. NIH [5T32HL007208-32]
  3. MGH ECOR
  4. Jane Coffin Childs postdoctoral fellowship
  5. Croucher Foundation
  6. GlaxoSmithKline Pharmaceuticals

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Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various somatic cell types, VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells.

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