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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Meis1 regulates postnatal cardiomyocyte cell cycle arrest
Nature, Volume 497, No. 7448, Year 2013
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Description
The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown. Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes, and for re-activation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16 and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration. © 2013 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Mahmoud, Ahmed I.
United States, Dallas
Ut Southwestern Medical School
Kocabas, Fatih
United States, Dallas
Ut Southwestern Medical School
Muralidhar, Shalini A.
United States, Dallas
Ut Southwestern Medical School
Kimura, Wataru
United States, Dallas
Ut Southwestern Medical School
Koura, Ahmed S.
Egypt, Cairo
Faculty of Medicine - Ain Shams University
Thet, Suwannee
United States, Dallas
Ut Southwestern Medical School
Porrello, Enzo R.
Australia, Brisbane
The University of Queensland
Sadek, Hesham A.
United States, Dallas
Ut Southwestern Medical School
Statistics
Citations: 484
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1038/nature12054
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Maternal And Child Health
Noncommunicable Diseases
Violence And Injury