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Heart repair by reprogramming non-myocytes with cardiac transcription factors
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 remodeling and susceptibility to arrhythmias. Cardiac fibroblasts account f...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367390/ https://www.ncbi.nlm.nih.gov/pubmed/22660318 http://dx.doi.org/10.1038/nature11139 |
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author | 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. |
author_facet | 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. |
author_sort | Song, Kunhua |
collection | PubMed |
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 remodeling 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 remodeling 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. |
format | Online Article Text |
id | pubmed-3367390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-33673902012-11-30 Heart repair by reprogramming non-myocytes with cardiac transcription factors 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. Nature Article 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 remodeling 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 remodeling 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. 2012-05-13 /pmc/articles/PMC3367390/ /pubmed/22660318 http://dx.doi.org/10.1038/nature11139 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article 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. Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title | Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title_full | Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title_fullStr | Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title_full_unstemmed | Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title_short | Heart repair by reprogramming non-myocytes with cardiac transcription factors |
title_sort | heart repair by reprogramming non-myocytes with cardiac transcription factors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367390/ https://www.ncbi.nlm.nih.gov/pubmed/22660318 http://dx.doi.org/10.1038/nature11139 |
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