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Heart repair by reprogramming non-myocytes with cardiac transcription factors.

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, HAND2, MEF2C and TBX5, can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodelling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.

Pubmed ID: 22660318

Authors

  • Song K
  • Nam YJ
  • Luo X
  • Qi X
  • Tan W
  • Huang GN
  • Acharya A
  • Smith CL
  • Tallquist MD
  • Neilson EG
  • Hill JA
  • Bassel-Duby R
  • Olson EN

Journal

Nature

Publication Data

May 31, 2012

Associated Grants

  • Agency: NHLBI NIH HHS, Id: K99 HL114738
  • Agency: NHLBI NIH HHS, Id: P50 HL061033
  • Agency: NIAMS NIH HHS, Id: R01 AR040339
  • Agency: NHLBI NIH HHS, Id: R01 HL053351
  • Agency: NHLBI NIH HHS, Id: R01 HL061544
  • Agency: NHLBI NIH HHS, Id: R01 HL077439
  • Agency: NHLBI NIH HHS, Id: R01 HL083371
  • Agency: NHLBI NIH HHS, Id: R01 HL093039
  • Agency: NHLBI NIH HHS, Id: R01 HL111665
  • Agency: NHLBI NIH HHS, Id: R37 HL053351
  • Agency: NCRR NIH HHS, Id: S10 RR019137

Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Lineage
  • Cell Transdifferentiation
  • Cellular Reprogramming
  • Fibroblasts
  • Heart
  • Mice
  • Myocardial Infarction
  • Myocardium
  • Myocytes, Cardiac
  • Phenotype
  • Regenerative Medicine
  • S100 Proteins
  • Tail
  • Transcription Factors