Meis1 regulates postnatal cardiomyocyte cell cycle arrest

Mahmoud, Ahmed I., Kocabas, Fatih, Muralidhar, Shalini A., Kimura, Wataru, Koura, Ahmed S., Thet, Suwannee, Porrello, Enzo R. and Sadek, Hesham A. (2013) Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature, 497 7448: 249-253. doi:10.1038/nature12054

Author Mahmoud, Ahmed I.
Kocabas, Fatih
Muralidhar, Shalini A.
Kimura, Wataru
Koura, Ahmed S.
Thet, Suwannee
Porrello, Enzo R.
Sadek, Hesham A.
Title Meis1 regulates postnatal cardiomyocyte cell cycle arrest
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2013-05-09
Year available 2013
Sub-type Article (original research)
DOI 10.1038/nature12054
Volume 497
Issue 7448
Start page 249
End page 253
Total pages 5
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2014
Language eng
Formatted abstract
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.
Keyword Zebrafish heart regeneration
Hematopoietic stem-cells
Cardiac myocytes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 100 times in Thomson Reuters Web of Science Article | Citations
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