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Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog
We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792153/ https://www.ncbi.nlm.nih.gov/pubmed/26975336 http://dx.doi.org/10.1038/srep23017 |
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author | Wang, Xiaowen Hodgkinson, Conrad P Lu, Kefeng Payne, Alan J Pratt, Richard E Dzau, Victor J |
author_facet | Wang, Xiaowen Hodgkinson, Conrad P Lu, Kefeng Payne, Alan J Pratt, Richard E Dzau, Victor J |
author_sort | Wang, Xiaowen |
collection | PubMed |
description | We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessary to develop new methodologies to overcome these limitations. Here, we report the identification of a specific media composition, reprogramming media (RM), which augmented the effect of miR combo by 5–15-fold depending upon the cardiac marker tested. RM alone was sufficient to strongly induce cardiac gene and protein expression in neonatal tail-tip as well as cardiac fibroblasts. Expression of pluripotency markers Nanog, Oct4, Sox2, and Klf4 was significantly enhanced by RM, with miR combo augmenting the effect further. Knockdown of Nanog by siRNA inhibited the effect of RM on cardiac gene expression. Removal of insulin-transferrin-selenium completely inhibited the effect of reprogramming media upon cardiac gene expression and the addition of selenium to standard culture media recapitulated the effects of RM. Moreover, selenium enhanced the reprogramming efficiency of miR combo. |
format | Online Article Text |
id | pubmed-4792153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47921532016-03-16 Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog Wang, Xiaowen Hodgkinson, Conrad P Lu, Kefeng Payne, Alan J Pratt, Richard E Dzau, Victor J Sci Rep Article We have recently shown that a combination of microRNAs, miR combo, can directly reprogram cardiac fibroblasts into functional cardiomyocytes in vitro and in vivo. However, direct reprogramming strategies are inefficient and slow. Moving towards the eventual goal of clinical application it is necessary to develop new methodologies to overcome these limitations. Here, we report the identification of a specific media composition, reprogramming media (RM), which augmented the effect of miR combo by 5–15-fold depending upon the cardiac marker tested. RM alone was sufficient to strongly induce cardiac gene and protein expression in neonatal tail-tip as well as cardiac fibroblasts. Expression of pluripotency markers Nanog, Oct4, Sox2, and Klf4 was significantly enhanced by RM, with miR combo augmenting the effect further. Knockdown of Nanog by siRNA inhibited the effect of RM on cardiac gene expression. Removal of insulin-transferrin-selenium completely inhibited the effect of reprogramming media upon cardiac gene expression and the addition of selenium to standard culture media recapitulated the effects of RM. Moreover, selenium enhanced the reprogramming efficiency of miR combo. Nature Publishing Group 2016-03-15 /pmc/articles/PMC4792153/ /pubmed/26975336 http://dx.doi.org/10.1038/srep23017 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Xiaowen Hodgkinson, Conrad P Lu, Kefeng Payne, Alan J Pratt, Richard E Dzau, Victor J Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title | Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title_full | Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title_fullStr | Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title_full_unstemmed | Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title_short | Selenium Augments microRNA Directed Reprogramming of Fibroblasts to Cardiomyocytes via Nanog |
title_sort | selenium augments microrna directed reprogramming of fibroblasts to cardiomyocytes via nanog |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792153/ https://www.ncbi.nlm.nih.gov/pubmed/26975336 http://dx.doi.org/10.1038/srep23017 |
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