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Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells

Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for im...

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Autores principales: Al-Maqtari, Tareq, Hong, Kyung U., Vajravelu, Bathri N., Moktar, Afsoon, Cao, Pengxiao, Moore, Joseph B., Bolli, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371315/
https://www.ncbi.nlm.nih.gov/pubmed/28355297
http://dx.doi.org/10.1371/journal.pone.0174242
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author Al-Maqtari, Tareq
Hong, Kyung U.
Vajravelu, Bathri N.
Moktar, Afsoon
Cao, Pengxiao
Moore, Joseph B.
Bolli, Roberto
author_facet Al-Maqtari, Tareq
Hong, Kyung U.
Vajravelu, Bathri N.
Moktar, Afsoon
Cao, Pengxiao
Moore, Joseph B.
Bolli, Roberto
author_sort Al-Maqtari, Tareq
collection PubMed
description Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C) into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy.
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spelling pubmed-53713152017-04-07 Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells Al-Maqtari, Tareq Hong, Kyung U. Vajravelu, Bathri N. Moktar, Afsoon Cao, Pengxiao Moore, Joseph B. Bolli, Roberto PLoS One Research Article Although transplantation of c-kit+ cardiac progenitor cells (CPCs) significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs). We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C) into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy. Public Library of Science 2017-03-29 /pmc/articles/PMC5371315/ /pubmed/28355297 http://dx.doi.org/10.1371/journal.pone.0174242 Text en © 2017 Al-Maqtari et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Al-Maqtari, Tareq
Hong, Kyung U.
Vajravelu, Bathri N.
Moktar, Afsoon
Cao, Pengxiao
Moore, Joseph B.
Bolli, Roberto
Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title_full Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title_fullStr Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title_full_unstemmed Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title_short Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
title_sort transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371315/
https://www.ncbi.nlm.nih.gov/pubmed/28355297
http://dx.doi.org/10.1371/journal.pone.0174242
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