Molecular barriers to direct cardiac reprogramming
Myocardial infarction afflicts close to three quarters of a million Americans annually, resulting in reduced heart function, arrhythmia, and frequently death. Cardiomyocyte death reduces the heart’s pump capacity while the deposition of a non-conductive scar incurs the risk of arrhythmia. Direct car...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Higher Education Press
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636745/ https://www.ncbi.nlm.nih.gov/pubmed/28389873 http://dx.doi.org/10.1007/s13238-017-0402-x |
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author | Vaseghi, Haley Liu, Jiandong Qian, Li |
author_facet | Vaseghi, Haley Liu, Jiandong Qian, Li |
author_sort | Vaseghi, Haley |
collection | PubMed |
description | Myocardial infarction afflicts close to three quarters of a million Americans annually, resulting in reduced heart function, arrhythmia, and frequently death. Cardiomyocyte death reduces the heart’s pump capacity while the deposition of a non-conductive scar incurs the risk of arrhythmia. Direct cardiac reprogramming emerged as a novel technology to simultaneously reduce scar tissue and generate new cardiomyocytes to restore cardiac function. This technology converts endogenous cardiac fibroblasts directly into induced cardiomyocyte-like cells using a variety of cocktails including transcription factors, microRNAs, and small molecules. Although promising, direct cardiac reprogramming is still in its fledging phase, and numerous barriers have to be overcome prior to its clinical application. This review discusses current findings to optimize reprogramming efficiency, including reprogramming factor cocktails and stoichiometry, epigenetic barriers to cell fate reprogramming, incomplete conversion and residual fibroblast identity, requisite growth factors, and environmental cues. Finally, we address the current challenges and future directions for the field. |
format | Online Article Text |
id | pubmed-5636745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Higher Education Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-56367452017-10-24 Molecular barriers to direct cardiac reprogramming Vaseghi, Haley Liu, Jiandong Qian, Li Protein Cell Review Myocardial infarction afflicts close to three quarters of a million Americans annually, resulting in reduced heart function, arrhythmia, and frequently death. Cardiomyocyte death reduces the heart’s pump capacity while the deposition of a non-conductive scar incurs the risk of arrhythmia. Direct cardiac reprogramming emerged as a novel technology to simultaneously reduce scar tissue and generate new cardiomyocytes to restore cardiac function. This technology converts endogenous cardiac fibroblasts directly into induced cardiomyocyte-like cells using a variety of cocktails including transcription factors, microRNAs, and small molecules. Although promising, direct cardiac reprogramming is still in its fledging phase, and numerous barriers have to be overcome prior to its clinical application. This review discusses current findings to optimize reprogramming efficiency, including reprogramming factor cocktails and stoichiometry, epigenetic barriers to cell fate reprogramming, incomplete conversion and residual fibroblast identity, requisite growth factors, and environmental cues. Finally, we address the current challenges and future directions for the field. Higher Education Press 2017-04-07 2017-10 /pmc/articles/PMC5636745/ /pubmed/28389873 http://dx.doi.org/10.1007/s13238-017-0402-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Review Vaseghi, Haley Liu, Jiandong Qian, Li Molecular barriers to direct cardiac reprogramming |
title | Molecular barriers to direct cardiac reprogramming |
title_full | Molecular barriers to direct cardiac reprogramming |
title_fullStr | Molecular barriers to direct cardiac reprogramming |
title_full_unstemmed | Molecular barriers to direct cardiac reprogramming |
title_short | Molecular barriers to direct cardiac reprogramming |
title_sort | molecular barriers to direct cardiac reprogramming |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636745/ https://www.ncbi.nlm.nih.gov/pubmed/28389873 http://dx.doi.org/10.1007/s13238-017-0402-x |
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