Publication Date:
2012-06-05
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367390/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367390/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Song, Kunhua -- Nam, Young-Jae -- Luo, Xiang -- Qi, Xiaoxia -- Tan, Wei -- Huang, Guo N -- Acharya, Asha -- Smith, Christopher L -- Tallquist, Michelle D -- Neilson, Eric G -- Hill, Joseph A -- Bassel-Duby, Rhonda -- Olson, Eric N -- K99 HL114738/HL/NHLBI NIH HHS/ -- P50 HL061033/HL/NHLBI NIH HHS/ -- R01 AR040339/AR/NIAMS NIH HHS/ -- R01 HL053351/HL/NHLBI NIH HHS/ -- R01 HL061544/HL/NHLBI NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL083371/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- R37 HL053351/HL/NHLBI NIH HHS/ -- S10 RR019137/RR/NCRR NIH HHS/ -- England -- Nature. 2012 May 13;485(7400):599-604. doi: 10.1038/nature11139.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9148, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22660318" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
;
Cell Lineage
;
*Cell Transdifferentiation
;
*Cellular Reprogramming
;
Fibroblasts/*cytology/physiology
;
Heart/*physiology/physiopathology
;
Mice
;
Myocardial Infarction/pathology/physiopathology/*therapy
;
Myocardium/cytology/pathology
;
Myocytes, Cardiac/*cytology/physiology
;
Phenotype
;
Regenerative Medicine/methods
;
S100 Proteins/genetics/metabolism
;
Tail/cytology
;
Transcription Factors/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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