Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice

Abstract Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A rec...

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Autores principales:	Ken Hashimoto, Aya Kodama, Takeshi Honda, Akira Hanashima, Yoshihiro Ujihara, Takashi Murayama, Shin-ichiro Nishimatsu, Satoshi Mohri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/242b9992acf4413aad88c35ca445c13d
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spelling	oai:doaj.org-article:242b9992acf4413aad88c35ca445c13d2021-12-02T12:32:58ZFam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice10.1038/s41598-017-04823-12045-2322https://doaj.org/article/242b9992acf4413aad88c35ca445c13d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04823-1https://doaj.org/toc/2045-2322Abstract Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A recent study has shown that this proliferation depends on a low fetal oxygen condition before the onset of breathing at birth. We have established an isolation protocol for mouse fetal cardiomyocytes, performed under strict low oxygen conditions to mimic the intrauterine environment, that gives the highest proliferative activities thus far reported. Oxygen exposure during isolation/culture markedly inhibited cell division and repressed cell cycle-promoting genes, and subsequent genome-wide analysis identified Fam64a as a novel regulatory molecule. Fam64a was abundantly expressed in hypoxic fetal cardiomyocyte nuclei, but this expression was drastically repressed by oxygen exposure, and in postnatal cardiomyocytes following the onset of breathing and the resulting elevation of oxygen tension. Fam64a knockdown inhibited and its overexpression enhanced cardiomyocyte proliferation. Expression of a non-degradable Fam64a mutant suggested that optimum Fam64a expression and subsequent degradation by anaphase-promoting complex/cyclosome (APC/C) during the metaphase-to-anaphase transition are required for fetal cardiomyocyte division. We propose that Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice.Ken HashimotoAya KodamaTakeshi HondaAkira HanashimaYoshihiro UjiharaTakashi MurayamaShin-ichiro NishimatsuSatoshi MohriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ken Hashimoto Aya Kodama Takeshi Honda Akira Hanashima Yoshihiro Ujihara Takashi Murayama Shin-ichiro Nishimatsu Satoshi Mohri Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
description	Abstract Fetal cardiomyocytes actively proliferate to form the primitive heart in utero in mammals, but they stop dividing shortly after birth. The identification of essential molecules maintaining this active cardiomyocyte proliferation is indispensable for potential adult heart regeneration. A recent study has shown that this proliferation depends on a low fetal oxygen condition before the onset of breathing at birth. We have established an isolation protocol for mouse fetal cardiomyocytes, performed under strict low oxygen conditions to mimic the intrauterine environment, that gives the highest proliferative activities thus far reported. Oxygen exposure during isolation/culture markedly inhibited cell division and repressed cell cycle-promoting genes, and subsequent genome-wide analysis identified Fam64a as a novel regulatory molecule. Fam64a was abundantly expressed in hypoxic fetal cardiomyocyte nuclei, but this expression was drastically repressed by oxygen exposure, and in postnatal cardiomyocytes following the onset of breathing and the resulting elevation of oxygen tension. Fam64a knockdown inhibited and its overexpression enhanced cardiomyocyte proliferation. Expression of a non-degradable Fam64a mutant suggested that optimum Fam64a expression and subsequent degradation by anaphase-promoting complex/cyclosome (APC/C) during the metaphase-to-anaphase transition are required for fetal cardiomyocyte division. We propose that Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice.
format	article
author	Ken Hashimoto Aya Kodama Takeshi Honda Akira Hanashima Yoshihiro Ujihara Takashi Murayama Shin-ichiro Nishimatsu Satoshi Mohri
author_facet	Ken Hashimoto Aya Kodama Takeshi Honda Akira Hanashima Yoshihiro Ujihara Takashi Murayama Shin-ichiro Nishimatsu Satoshi Mohri
author_sort	Ken Hashimoto
title	Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title_short	Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title_full	Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title_fullStr	Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title_full_unstemmed	Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title_sort	fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/242b9992acf4413aad88c35ca445c13d
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Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice

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