title: Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5.
abstract: BACKGROUND
  Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown.
  
  
  OBJECTIVE
  To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT).
  
  
  RESULTS
  We induced GMT overexpression in murine tail tip fibroblasts (TTFs) and cardiac fibroblasts (CFs) from multiple lines of transgenic mice carrying different cardiomyocyte lineage reporters. We found that the induction of GMT overexpression in TTFs and CFs is inefficient at inducing molecular and electrophysiological phenotypes of mature cardiomyocytes. In addition, transplantation of GMT infected CFs into injured mouse hearts resulted in decreased cell survival with minimal induction of cardiomyocyte genes.
  
  
  CONCLUSIONS
  Significant challenges remain in our ability to convert fibroblasts into cardiomyocyte-like cells and a greater understanding of cardiovascular epigenetics is needed to increase the translational potential of this strategy.
authors.affiliation: Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, USA.
authors.forename: Jenny X
authors.initials: JX
authors.lastname: Chen
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
authors.forename: Marcus-Andre
authors.initials: MA
authors.lastname: Deutsch
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Moshe
authors.initials: M
authors.lastname: Rav-Acha
authors.forename: Serge
authors.initials: S
authors.lastname: Gregoire
authors.forename: Marc C
authors.initials: MC
authors.lastname: Engels
authors.forename: Kuppusamy
authors.initials: K
authors.lastname: Rajarajan
authors.forename: Ravi
authors.initials: R
authors.lastname: Karra
authors.forename: E Dale
authors.initials: ED
authors.lastname: Abel
authors.forename: Joe C
authors.initials: JC
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Milan
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wu
mesh_terms: D000200:Action Potentials; D000818:Animals; D019070:Cell Lineage; D002470:Cell Survival; D054338:Cell Transdifferentiation / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D064326:MEF2 Transcription Factors; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000637:transplantation; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
chemical_list: D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5