Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain
Open Access
- 20 June 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 100 (1), 105-113
- https://doi.org/10.1093/cvr/cvt167
Abstract
Fibroblasts can be directly reprogrammed to cardiomyocyte-like cells by introducing defined genes. However, the reprogramming efficiency remains low, delaying the clinical application of this strategy to regenerative cardiology. We previously showed that fusion of the MyoD transactivation domain to the pluripotency transcription factor Oct4 facilitated the transcriptional activity of Oct4, resulting in highly efficient production of induced pluripotent stem cells. We examined whether the same approach can be applied to cardiac transcription factors to facilitate cardiac reprogramming. We fused the MyoD domain to Mef2c, Gata4, Hand2, and Tbx5 and transduced these genes in various combinations into mouse non-cardiac fibroblasts. Transduction of the chimeric Mef2c with the wild-types of the other three genes produced much larger beating clusters of cardiomyocyte-like cells faster than the combination of the four wild-type genes, with an efficiency of 3.5%, >15-fold greater than the wild-type genes. Fusion of a powerful transactivation domain to heterologous factors can increase the efficiency of direct reprogramming of fibroblasts to cardiomyocytes.This publication has 36 references indexed in Scilit:
- Transcription factors ETS2 and MESP1 transdifferentiate human dermal fibroblasts into cardiac progenitorsProceedings of the National Academy of Sciences of the United States of America, 2012
- Heart repair by reprogramming non-myocytes with cardiac transcription factorsNature, 2012
- In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytesNature, 2012
- Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct ReprogrammingCell Stem Cell, 2012
- Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling with the Transactivation Domain of MyoDThe International Journal of Cell Cloning, 2011
- Direct Reprogramming of Fibroblasts into Functional Cardiomyocytes by Defined FactorsCell, 2010
- Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cellsNature Biotechnology, 2010
- Epigenetic memory in induced pluripotent stem cellsNature, 2010
- Physical Interaction between TBX5 and MEF2C Is Required for Early Heart DevelopmentMolecular and Cellular Biology, 2009
- Plat-E: an efficient and stable system for transient packaging of retrovirusesGene Therapy, 2000