Heart repair by reprogramming non-myocytes with cardiac transcription factors

By Kunhua Song, Y. Nam, Xiang Luo, X. Qi, W. Tan, Guo N. Huang, Asha Acharya, Christopher L. Smith, M. Tallquist, Eric G. Neilson and 3 more. Nature, 2012

1,160 citations recorded by the source corpus.

The adult mammalian heart possesses little regenerative potential following injury. Fibrosis due to activation of cardiac fibroblasts impedes cardiac regeneration and contributes to loss of contractile function, pathological remodelling and susceptibility to arrhythmias. Cardiac fibroblasts account for a majority of cells in the heart and represent a potential cellular source for restoration of cardiac function following injury through phenotypic reprogramming to a myocardial cell fate. Here we show that four transcription factors, GATA4, HAND2, MEF2C and TBX5, can cooperatively reprogram adult mouse tail-tip and cardiac fibroblasts into beating cardiac-like myocytes in vitro. Forced expression of these factors in dividing non-cardiomyocytes in mice reprograms these cells into functional cardiac-like myocytes, improves cardiac function and reduces adverse ventricular remodelling following myocardial infarction. Our results suggest a strategy for cardiac repair through reprogramming fibroblasts resident in the heart with cardiogenic transcription factors or other molecules.

Subfields: Cardiology and Cardiovascular Medicine, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/225509f61a4efee39f3f1a487efdeca6ff97d9f6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cardiology and Cardiovascular Medicine

1. Nikolaos G. Frangogiannis
2. E. Olson

In Molecular Biology

1. Nikolaos G. Frangogiannis
2. E. Olson
3. J. Richardson
4. R. Bassel-Duby
5. X. Qi
6. L. Sutherland
7. Charles E. Murry
8. David P. Bartel

In Surgery

1. Nikolaos G. Frangogiannis
2. Nadia A. Rosenthal
3. Charles E. Murry

Citations in the corpus

• Pathophysiology of Myocardial Infarction (2015, positive): “diomyocytes have suggested exciting novel therapeutic strategies for cardiac regeneration (339).”
• Engineering Adolescence: Maturation of Human Pluripotent Stem Cell-derived Cardiomyocytes (2014, background): “When reprogramming was performed in vivo,(112,115) however, the induced cardiomyocytes displayed morphological and functional properties of adult cardiomyocytes with elongated cell shape, intercalated disks with polarized connexin 43 expression, and electrophysiological parameters similar to the adu”
• Hippo pathway effector Yap promotes cardiac regeneration (2013, methodology): “MI surgeries performed on neonatal mice at P1 and P7 and on adult mice were performed as described previously (6, 14) and in SI Materials and Methods.”
• Revisiting Cardiac Cellular Composition (2015, background): “In the Tcf21 mouse model, resident fibroblasts and their descendants are indelibly tagged with tdTomato fluorescence after Cre induction.(15,31) We induced Cre-mediated recombination at either embryonic day 16.”
• Dynamic and Coordinated Epigenetic Regulation of Developmental Transitions in the Cardiac Lineage (2012, neutral): “These insights will be valuable to develop improved cardiac reprogramming strategies (Ieda et al., 2010; Qian et al., 2012; Song et al., 2012; Takeuchi and Bruneau, 2009) and to elucidate how disruption of these diverse regulatory modules contributes to congenital heart disease.”