TY - JOUR
T1 - Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5.
AU - Chen, Jenny X.
AU - Krane, Markus
AU - Deutsch, Marcus Andre
AU - Wang, L.
AU - Rav-Acha, Moshe
AU - Gregoire, Serge
AU - Engels, Marc C.
AU - Rajarajan, Kuppusamy
AU - Karra, Ravi
AU - Abel, E. Dale
AU - Wu, Joe C.
AU - Milan, David
AU - Wu, Sean M.
PY - 2012/6/22
Y1 - 2012/6/22
N2 - Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). 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. 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.
AB - Direct reprogramming of fibroblasts into cardiomyocytes is a novel strategy for cardiac regeneration. However, the key determinants involved in this process are unknown. To assess the efficiency of direct fibroblast reprogramming via viral overexpression of GATA4, Mef2c, and Tbx5 (GMT). 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=85027957068&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.112.270264
DO - 10.1161/CIRCRESAHA.112.270264
M3 - Article
C2 - 22581928
AN - SCOPUS:85027957068
SN - 0009-7330
VL - 111
SP - 50
EP - 55
JO - Circulation Research
JF - Circulation Research
IS - 1
ER -