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Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies
The mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury. Several reports have demonstrated that mononucleated cardiomyocytes are more responsive than are binucleated cardiomyocytes to proprolife...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194103/ https://www.ncbi.nlm.nih.gov/pubmed/32130910 http://dx.doi.org/10.1016/j.celrep.2020.02.034 |
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author | Windmueller, Rebecca Leach, John P. Babu, Apoorva Zhou, Su Morley, Michael P. Wakabayashi, Aoi Petrenko, Nataliya B. Viatour, Patrick Morrisey, Edward E. |
author_facet | Windmueller, Rebecca Leach, John P. Babu, Apoorva Zhou, Su Morley, Michael P. Wakabayashi, Aoi Petrenko, Nataliya B. Viatour, Patrick Morrisey, Edward E. |
author_sort | Windmueller, Rebecca |
collection | PubMed |
description | The mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury. Several reports have demonstrated that mononucleated cardiomyocytes are more responsive than are binucleated cardiomyocytes to proproliferative stimuli. We have developed a strategy to isolate and characterize highly enriched populations of mononucleated and binucleated cardiomyocytes at various times of development. Our results suggest that an E2f/Rb transcriptional network is central to the divergence of these two populations and that remnants of the differences acquired during the neonatal period remain in adult cardiomyocytes. Moreover, inducing binucleation by genetically blocking the ability of cardiomyocytes to complete cytokinesis leads to a reduction in E2f target gene expression, directly linking the E2f pathway with nucleation. These data identify key molecular differences between mononucleated and binucleated mammalian cardiomyocytes that can be used to leverage cardiomyocyte proliferation for promoting injury repair in the heart. |
format | Online Article Text |
id | pubmed-7194103 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-71941032020-05-01 Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies Windmueller, Rebecca Leach, John P. Babu, Apoorva Zhou, Su Morley, Michael P. Wakabayashi, Aoi Petrenko, Nataliya B. Viatour, Patrick Morrisey, Edward E. Cell Rep Article The mammalian heart is incapable of regenerating a sufficient number of cardiomyocytes to ameliorate the loss of contractile muscle after acute myocardial injury. Several reports have demonstrated that mononucleated cardiomyocytes are more responsive than are binucleated cardiomyocytes to proproliferative stimuli. We have developed a strategy to isolate and characterize highly enriched populations of mononucleated and binucleated cardiomyocytes at various times of development. Our results suggest that an E2f/Rb transcriptional network is central to the divergence of these two populations and that remnants of the differences acquired during the neonatal period remain in adult cardiomyocytes. Moreover, inducing binucleation by genetically blocking the ability of cardiomyocytes to complete cytokinesis leads to a reduction in E2f target gene expression, directly linking the E2f pathway with nucleation. These data identify key molecular differences between mononucleated and binucleated mammalian cardiomyocytes that can be used to leverage cardiomyocyte proliferation for promoting injury repair in the heart. 2020-03-03 /pmc/articles/PMC7194103/ /pubmed/32130910 http://dx.doi.org/10.1016/j.celrep.2020.02.034 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Windmueller, Rebecca Leach, John P. Babu, Apoorva Zhou, Su Morley, Michael P. Wakabayashi, Aoi Petrenko, Nataliya B. Viatour, Patrick Morrisey, Edward E. Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title | Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title_full | Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title_fullStr | Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title_full_unstemmed | Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title_short | Direct Comparison of Mononucleated and Binucleated Cardiomyocytes Reveals Molecular Mechanisms Underlying Distinct Proliferative Competencies |
title_sort | direct comparison of mononucleated and binucleated cardiomyocytes reveals molecular mechanisms underlying distinct proliferative competencies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194103/ https://www.ncbi.nlm.nih.gov/pubmed/32130910 http://dx.doi.org/10.1016/j.celrep.2020.02.034 |
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