Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

Abstract After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thu...

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Autores principales:	David C. Zebrowski, Charlotte H. Jensen, Robert Becker, Fulvia Ferrazzi, Christina Baun, Svend Hvidsten, Søren P. Sheikh, Brian D. Polizzotti, Ditte C. Andersen, Felix B. Engel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7d8aee405594a0083d3e1c9ea9c1ef3
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spelling	oai:doaj.org-article:e7d8aee405594a0083d3e1c9ea9c1ef32021-12-02T16:07:48ZCardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation10.1038/s41598-017-08947-22045-2322https://doaj.org/article/e7d8aee405594a0083d3e1c9ea9c1ef32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08947-2https://doaj.org/toc/2045-2322Abstract After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic.David C. ZebrowskiCharlotte H. JensenRobert BeckerFulvia FerrazziChristina BaunSvend HvidstenSøren P. SheikhBrian D. PolizzottiDitte C. AndersenFelix B. EngelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David C. Zebrowski Charlotte H. Jensen Robert Becker Fulvia Ferrazzi Christina Baun Svend Hvidsten Søren P. Sheikh Brian D. Polizzotti Ditte C. Andersen Felix B. Engel Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
description	Abstract After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold increased rate of binucleation there was a nearly 2-fold increase in the number of cardiomyocytes in mitosis indicating that the majority of injury-induced cardiomyocyte cell cycle activity results in binucleation, not proliferation. Concurrently, cardiomyocytes undergoing cytokinesis from embryonic hearts exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion. Collectively, these data suggest that should a regenerative program exist in the newborn mammalian heart, it is quickly curtailed by developmental mechanisms that render cardiomyocytes post-mitotic.
format	article
author	David C. Zebrowski Charlotte H. Jensen Robert Becker Fulvia Ferrazzi Christina Baun Svend Hvidsten Søren P. Sheikh Brian D. Polizzotti Ditte C. Andersen Felix B. Engel
author_facet	David C. Zebrowski Charlotte H. Jensen Robert Becker Fulvia Ferrazzi Christina Baun Svend Hvidsten Søren P. Sheikh Brian D. Polizzotti Ditte C. Andersen Felix B. Engel
author_sort	David C. Zebrowski
title	Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
title_short	Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
title_full	Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
title_fullStr	Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
title_full_unstemmed	Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
title_sort	cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e7d8aee405594a0083d3e1c9ea9c1ef3
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Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

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