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...

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Autores principales: Vaseghi, Haley, Liu, Jiandong, Qian, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Higher Education Press 2017
Materias:
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.
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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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