Meis1 regulates postnatal cardiomyocyte cell cycle arrest

Shalini A. Muralidhar, Hesham A. Sadek

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation (Porrello et al, Science 331:1078- 1080, 2011; Proc Natl Acad Sci U S A 110:187-92, 2013). 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 (Paige et al, Cell 151:221-232, 2012; Wamstad et al, Cell 151: 206-220, 2012). 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 reactivation 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.

Original languageEnglish (US)
Title of host publicationEtiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology
PublisherSpringer Japan
Pages93-101
Number of pages9
ISBN (Electronic)9784431546283
ISBN (Print)9784431546276
DOIs
StatePublished - Jan 1 2016

Fingerprint

Cell Cycle Checkpoints
Cardiac Myocytes
Cells
Regeneration
Transcription Factors
Chemical activation
Mitosis
Muscle Cells
Transcriptional Activation
Cell Cycle
Wounds and Injuries

Keywords

  • Cardiomyocytes
  • Cell cycle
  • Heart injury
  • Meis1
  • Regeneration

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Muralidhar, S. A., & Sadek, H. A. (2016). Meis1 regulates postnatal cardiomyocyte cell cycle arrest. In Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology (pp. 93-101). Springer Japan. https://doi.org/10.1007/978-4-431-54628-3_11

Meis1 regulates postnatal cardiomyocyte cell cycle arrest. / Muralidhar, Shalini A.; Sadek, Hesham A.

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, 2016. p. 93-101.

Research output: Chapter in Book/Report/Conference proceedingChapter

Muralidhar, SA & Sadek, HA 2016, Meis1 regulates postnatal cardiomyocyte cell cycle arrest. in Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, pp. 93-101. https://doi.org/10.1007/978-4-431-54628-3_11
Muralidhar SA, Sadek HA. Meis1 regulates postnatal cardiomyocyte cell cycle arrest. In Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan. 2016. p. 93-101 https://doi.org/10.1007/978-4-431-54628-3_11
Muralidhar, Shalini A. ; Sadek, Hesham A. / Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology. Springer Japan, 2016. pp. 93-101
@inbook{2e1d393337d4437bb3ec6f6290cea51a,
title = "Meis1 regulates postnatal cardiomyocyte cell cycle arrest",
abstract = "The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation (Porrello et al, Science 331:1078- 1080, 2011; Proc Natl Acad Sci U S A 110:187-92, 2013). 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 (Paige et al, Cell 151:221-232, 2012; Wamstad et al, Cell 151: 206-220, 2012). 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 reactivation 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.",
keywords = "Cardiomyocytes, Cell cycle, Heart injury, Meis1, Regeneration",
author = "Muralidhar, {Shalini A.} and Sadek, {Hesham A.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/978-4-431-54628-3_11",
language = "English (US)",
isbn = "9784431546276",
pages = "93--101",
booktitle = "Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology",
publisher = "Springer Japan",

}

TY - CHAP

T1 - Meis1 regulates postnatal cardiomyocyte cell cycle arrest

AU - Muralidhar, Shalini A.

AU - Sadek, Hesham A.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation (Porrello et al, Science 331:1078- 1080, 2011; Proc Natl Acad Sci U S A 110:187-92, 2013). 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 (Paige et al, Cell 151:221-232, 2012; Wamstad et al, Cell 151: 206-220, 2012). 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 reactivation 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.

AB - The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation (Porrello et al, Science 331:1078- 1080, 2011; Proc Natl Acad Sci U S A 110:187-92, 2013). 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 (Paige et al, Cell 151:221-232, 2012; Wamstad et al, Cell 151: 206-220, 2012). 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 reactivation 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.

KW - Cardiomyocytes

KW - Cell cycle

KW - Heart injury

KW - Meis1

KW - Regeneration

UR - http://www.scopus.com/inward/record.url?scp=85006789697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006789697&partnerID=8YFLogxK

U2 - 10.1007/978-4-431-54628-3_11

DO - 10.1007/978-4-431-54628-3_11

M3 - Chapter

AN - SCOPUS:85006789697

SN - 9784431546276

SP - 93

EP - 101

BT - Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

PB - Springer Japan

ER -