Journal article
Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5
Circulation research, Vol.111(1), pp.50-55
06/22/2012
DOI: 10.1161/CIRCRESAHA.112.270264
PMCID: PMC3390172
PMID: 22581928
Abstract
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.
Details
- Title: Subtitle
- Inefficient Reprogramming of Fibroblasts into Cardiomyocytes Using Gata4, Mef2c, and Tbx5
- Creators
- Jenny ChenMarkus KraneMarcus-Andre DeutschLi WangMoshe Rav-AchaSerge GregoireMarc EngelsKuppusamy RajarajanRavi KarraE AbelJoe WuDavid MilanSean Wu
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.111(1), pp.50-55
- Publisher
- American Heart Association, Inc
- DOI
- 10.1161/CIRCRESAHA.112.270264
- PMID
- 22581928
- PMCID
- PMC3390172
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 06/22/2012
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025274302771
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