Dedifferentiation and proliferation of mammalian cardiomyocytes.

<h4>Background</h4>It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.<h4>Me...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yiqiang Zhang, Tao-Sheng Li, Shuo-Tsan Lee, Kolja A Wawrowsky, Ke Cheng, Giselle Galang, Konstantinos Malliaras, M Roselle Abraham, Charles Wang, Eduardo Marbán
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ce886306d9044c3900d9ece50b203ee
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3ce886306d9044c3900d9ece50b203ee
record_format	dspace
spelling	oai:doaj.org-article:3ce886306d9044c3900d9ece50b203ee2021-11-18T06:35:26ZDedifferentiation and proliferation of mammalian cardiomyocytes.1932-620310.1371/journal.pone.0012559https://doaj.org/article/3ce886306d9044c3900d9ece50b203ee2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838637/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.<h4>Methodology/principal findings</h4>Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1) cardiomyocyte purification from rat hearts, and 2) genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs), while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP) continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+).<h4>Conclusions/significance</h4>Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness, including the expression of c-kit and the capacity for multipotency.Yiqiang ZhangTao-Sheng LiShuo-Tsan LeeKolja A WawrowskyKe ChengGiselle GalangKonstantinos MalliarasM Roselle AbrahamCharles WangEduardo MarbánPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12559 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yiqiang Zhang Tao-Sheng Li Shuo-Tsan Lee Kolja A Wawrowsky Ke Cheng Giselle Galang Konstantinos Malliaras M Roselle Abraham Charles Wang Eduardo Marbán Dedifferentiation and proliferation of mammalian cardiomyocytes.
description	<h4>Background</h4>It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.<h4>Methodology/principal findings</h4>Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1) cardiomyocyte purification from rat hearts, and 2) genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs), while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP) continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+).<h4>Conclusions/significance</h4>Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness, including the expression of c-kit and the capacity for multipotency.
format	article
author	Yiqiang Zhang Tao-Sheng Li Shuo-Tsan Lee Kolja A Wawrowsky Ke Cheng Giselle Galang Konstantinos Malliaras M Roselle Abraham Charles Wang Eduardo Marbán
author_facet	Yiqiang Zhang Tao-Sheng Li Shuo-Tsan Lee Kolja A Wawrowsky Ke Cheng Giselle Galang Konstantinos Malliaras M Roselle Abraham Charles Wang Eduardo Marbán
author_sort	Yiqiang Zhang
title	Dedifferentiation and proliferation of mammalian cardiomyocytes.
title_short	Dedifferentiation and proliferation of mammalian cardiomyocytes.
title_full	Dedifferentiation and proliferation of mammalian cardiomyocytes.
title_fullStr	Dedifferentiation and proliferation of mammalian cardiomyocytes.
title_full_unstemmed	Dedifferentiation and proliferation of mammalian cardiomyocytes.
title_sort	dedifferentiation and proliferation of mammalian cardiomyocytes.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/3ce886306d9044c3900d9ece50b203ee
work_keys_str_mv	AT yiqiangzhang dedifferentiationandproliferationofmammaliancardiomyocytes AT taoshengli dedifferentiationandproliferationofmammaliancardiomyocytes AT shuotsanlee dedifferentiationandproliferationofmammaliancardiomyocytes AT koljaawawrowsky dedifferentiationandproliferationofmammaliancardiomyocytes AT kecheng dedifferentiationandproliferationofmammaliancardiomyocytes AT gisellegalang dedifferentiationandproliferationofmammaliancardiomyocytes AT konstantinosmalliaras dedifferentiationandproliferationofmammaliancardiomyocytes AT mroselleabraham dedifferentiationandproliferationofmammaliancardiomyocytes AT charleswang dedifferentiationandproliferationofmammaliancardiomyocytes AT eduardomarban dedifferentiationandproliferationofmammaliancardiomyocytes
_version_	1718424408667717632

Dedifferentiation and proliferation of mammalian cardiomyocytes.

Ejemplares similares