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Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration

Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed...

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Autores principales: Cheng, Yuan‐Yuan, Yan, Yu‐Ting, Lundy, David J, Lo, Annie HA, Wang, Yu‐Ping, Ruan, Shu‐Chian, Lin, Po‐Ju, Hsieh, Patrick CH
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286362/
https://www.ncbi.nlm.nih.gov/pubmed/28011860
http://dx.doi.org/10.15252/emmm.201606558
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author Cheng, Yuan‐Yuan
Yan, Yu‐Ting
Lundy, David J
Lo, Annie HA
Wang, Yu‐Ping
Ruan, Shu‐Chian
Lin, Po‐Ju
Hsieh, Patrick CH
author_facet Cheng, Yuan‐Yuan
Yan, Yu‐Ting
Lundy, David J
Lo, Annie HA
Wang, Yu‐Ping
Ruan, Shu‐Chian
Lin, Po‐Ju
Hsieh, Patrick CH
author_sort Cheng, Yuan‐Yuan
collection PubMed
description Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up‐regulation of several mitosis‐related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3‐shRNA (FIJs), induced CMs to re‐enter the cell cycle and complete mitosis and cytokinesis in vitro. More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues.
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spelling pubmed-52863622017-02-03 Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration Cheng, Yuan‐Yuan Yan, Yu‐Ting Lundy, David J Lo, Annie HA Wang, Yu‐Ping Ruan, Shu‐Chian Lin, Po‐Ju Hsieh, Patrick CH EMBO Mol Med Research Articles Although remnant cardiomyocytes (CMs) possess a certain degree of proliferative ability, efficiency is too low for cardiac regeneration after injury. In this study, we identified a distinct stage within the initiation phase of CM reprogramming before the MET process, and microarray analysis revealed the strong up‐regulation of several mitosis‐related genes at this stage of reprogramming. Several candidate genes were selected and tested for their ability to induce CM proliferation. Delivering a cocktail of three genes, FoxM1, Id1, and Jnk3‐shRNA (FIJs), induced CMs to re‐enter the cell cycle and complete mitosis and cytokinesis in vitro. More importantly, this gene cocktail increased CM proliferation in vivo and significantly improved cardiac function and reduced fibrosis after myocardial infarction. Collectively, our findings present a cocktail FIJs that may be useful in cardiac regeneration and also provide a practical strategy for probing reprogramming assays for regeneration of other tissues. John Wiley and Sons Inc. 2016-12-23 2017-02 /pmc/articles/PMC5286362/ /pubmed/28011860 http://dx.doi.org/10.15252/emmm.201606558 Text en © 2016 Academia Sinica. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Cheng, Yuan‐Yuan
Yan, Yu‐Ting
Lundy, David J
Lo, Annie HA
Wang, Yu‐Ping
Ruan, Shu‐Chian
Lin, Po‐Ju
Hsieh, Patrick CH
Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title_full Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title_fullStr Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title_full_unstemmed Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title_short Reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
title_sort reprogramming‐derived gene cocktail increases cardiomyocyte proliferation for heart regeneration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286362/
https://www.ncbi.nlm.nih.gov/pubmed/28011860
http://dx.doi.org/10.15252/emmm.201606558
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