Conversion of human fibroblasts into functional cardiomyocytes by small molecules

Science. 2016 Jun 3;352(6290):1216-20. doi: 10.1126/science.aaf1502. Epub 2016 Apr 28.


Reprogramming somatic fibroblasts into alternative lineages would provide a promising source of cells for regenerative therapy. However, transdifferentiating human cells into specific homogeneous, functional cell types is challenging. Here we show that cardiomyocyte-like cells can be generated by treating human fibroblasts with a combination of nine compounds that we term 9C. The chemically induced cardiomyocyte-like cells uniformly contracted and resembled human cardiomyocytes in their transcriptome, epigenetic, and electrophysiological properties. 9C treatment of human fibroblasts resulted in a more open-chromatin conformation at key heart developmental genes, enabling their promoters and enhancers to bind effectors of major cardiogenic signals. When transplanted into infarcted mouse hearts, 9C-treated fibroblasts were efficiently converted to chemically induced cardiomyocyte-like cells. This pharmacological approach to lineage-specific reprogramming may have many important therapeutic implications after further optimization to generate mature cardiac cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Lineage / drug effects
  • Cell Lineage / genetics
  • Cell Transdifferentiation
  • Cellular Reprogramming / drug effects*
  • Cellular Reprogramming Techniques*
  • Chromatin / chemistry
  • Chromatin / metabolism
  • Disease Models, Animal
  • Fibroblasts / cytology
  • Fibroblasts / drug effects*
  • Heart / embryology
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Myocardial Infarction / surgery
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / transplantation
  • Myosin Heavy Chains / genetics
  • Organogenesis / genetics
  • Protein Conformation
  • Skin / cytology
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Transcriptome
  • Transduction, Genetic


  • Chromatin
  • Small Molecule Libraries
  • Myosin Heavy Chains