• Jenny X Chen, Markus Krane, Marcus-Andre Deutsch, Li Wang, Moshe Rav-Acha, Serge Gregoire, Marc C Engels, Kuppusamy Rajarajan, Ravi Karra, E Dale Abel, Joe C Wu, David Milan, and Sean M Wu.
• Cardiovascular Research Center, Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, USA.
• Circ. Res. 2012 Jun 22; 111 (1): 50-5.

RationaleDirect reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown.ObjectiveTo assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT).Methods And ResultsWe 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.ConclusionsSignificant 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.

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