RATIONALE: 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).
METHODS AND 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.