Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.

In contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forc...

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Autores principales:	Thomas Kisby, Irene de Lázaro, Maria Stylianou, Giulio Cossu, Kostas Kostarelos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4d0100f9e6fa43aba8eda8ba02a54f1d
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spelling	oai:doaj.org-article:4d0100f9e6fa43aba8eda8ba02a54f1d2021-11-25T05:54:20ZTransient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.1932-620310.1371/journal.pone.0251054https://doaj.org/article/4d0100f9e6fa43aba8eda8ba02a54f1d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251054https://doaj.org/toc/1932-6203In contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forced expression of Oct3/4, Sox2, Klf4 and c-Myc (OSKM). Here, we aimed to induce transient reprogramming of mammalian cardiomyocytes in vitro utilising an OSKM-encoding non-integrating vector. Reprogramming factor expression in postnatal rat and mouse cardiomyocytes triggered rapid but limited cell dedifferentiation. Concomitantly, a significant increase in cell viability, cell cycle related gene expression and Ki67 positive cells was observed consistent with an enhanced cell cycle activation. The transient nature of this partial reprogramming was confirmed as cardiomyocyte-specific cell morphology, gene expression and contractile activity were spontaneously recovered by day 15 after viral transduction. This study provides the first evidence that adenoviral OSKM delivery can induce partial reprogramming of postnatal cardiomyocytes. Therefore, adenoviral mediated transient reprogramming could be a novel and feasible strategy to recapitulate the regenerative mechanisms of lower vertebrates.Thomas KisbyIrene de LázaroMaria StylianouGiulio CossuKostas KostarelosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251054 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
description	In contrast to mammals, lower vertebrates are capable of extraordinary myocardial regeneration thanks to the ability of their cardiomyocytes to undergo transient dedifferentiation and proliferation. Somatic cells can be temporarily reprogrammed to a proliferative, dedifferentiated state through forced expression of Oct3/4, Sox2, Klf4 and c-Myc (OSKM). Here, we aimed to induce transient reprogramming of mammalian cardiomyocytes in vitro utilising an OSKM-encoding non-integrating vector. Reprogramming factor expression in postnatal rat and mouse cardiomyocytes triggered rapid but limited cell dedifferentiation. Concomitantly, a significant increase in cell viability, cell cycle related gene expression and Ki67 positive cells was observed consistent with an enhanced cell cycle activation. The transient nature of this partial reprogramming was confirmed as cardiomyocyte-specific cell morphology, gene expression and contractile activity were spontaneously recovered by day 15 after viral transduction. This study provides the first evidence that adenoviral OSKM delivery can induce partial reprogramming of postnatal cardiomyocytes. Therefore, adenoviral mediated transient reprogramming could be a novel and feasible strategy to recapitulate the regenerative mechanisms of lower vertebrates.
format	article
author	Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos
author_facet	Thomas Kisby Irene de Lázaro Maria Stylianou Giulio Cossu Kostas Kostarelos
author_sort	Thomas Kisby
title	Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
title_short	Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
title_full	Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
title_fullStr	Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
title_full_unstemmed	Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
title_sort	transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4d0100f9e6fa43aba8eda8ba02a54f1d
work_keys_str_mv	AT thomaskisby transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT irenedelazaro transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT mariastylianou transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT giuliocossu transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate AT kostaskostarelos transientreprogrammingofpostnatalcardiomyocytestoadedifferentiatedstate
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Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state.

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