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

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...

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Autores principales: Hashimoto, Ken, Kodama, Aya, Honda, Takeshi, Hanashima, Akira, Ujihara, Yoshihiro, Murayama, Takashi, Nishimatsu, Shin-ichiro, Mohri, Satoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493652/
https://www.ncbi.nlm.nih.gov/pubmed/28667270
http://dx.doi.org/10.1038/s41598-017-04823-1
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author Hashimoto, Ken
Kodama, Aya
Honda, Takeshi
Hanashima, Akira
Ujihara, Yoshihiro
Murayama, Takashi
Nishimatsu, Shin-ichiro
Mohri, Satoshi
author_facet Hashimoto, Ken
Kodama, Aya
Honda, Takeshi
Hanashima, Akira
Ujihara, Yoshihiro
Murayama, Takashi
Nishimatsu, Shin-ichiro
Mohri, Satoshi
author_sort Hashimoto, Ken
collection PubMed
description 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.
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spelling pubmed-54936522017-07-05 Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice Hashimoto, Ken Kodama, Aya Honda, Takeshi Hanashima, Akira Ujihara, Yoshihiro Murayama, Takashi Nishimatsu, Shin-ichiro Mohri, Satoshi Sci Rep Article 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. Nature Publishing Group UK 2017-06-30 /pmc/articles/PMC5493652/ /pubmed/28667270 http://dx.doi.org/10.1038/s41598-017-04823-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hashimoto, Ken
Kodama, Aya
Honda, Takeshi
Hanashima, Akira
Ujihara, Yoshihiro
Murayama, Takashi
Nishimatsu, Shin-ichiro
Mohri, Satoshi
Fam64a is a novel cell cycle promoter of hypoxic fetal cardiomyocytes in mice
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493652/
https://www.ncbi.nlm.nih.gov/pubmed/28667270
http://dx.doi.org/10.1038/s41598-017-04823-1
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