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Updated: Aug 2, 2025
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Visualization of Cell Cycle Variations and Determination of Nucleation in Postnatal Cardiomyocytes
Published on: February 24, 2017
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Btg1 and Btg2 regulate neonatal cardiomyocyte cell cycle arrest
Nivedhitha Velayutham1, Maria Uscategui Calderon1, Christina M Alfieri2
1Molecular and Developmental Biology Graduate Program, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA; The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Journal of Molecular and Cellular Cardiology
|April 16, 2023
Summary
Transcriptional co-regulators Btg1 and Btg2 (B-cell translocation gene 2) contribute to cardiomyocyte cell cycle arrest after birth in mice. Their absence leads to increased mitotic activity in neonatal hearts.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Molecular Genetics
Background:
- Rodent cardiomyocytes naturally arrest cell division in the first postnatal week.
- The molecular mechanisms regulating this critical developmental transition remain incompletely understood.
Purpose of the Study:
- To investigate the role of transcriptional co-regulators Btg1 and Btg2 in postnatal cardiomyocyte cell cycle arrest and maturation.
- To determine if Btg1/2 influence cardiomyocyte proliferation and cell cycle exit.
Main Methods:
- Utilized Btg1/2 constitutive double knockout (DKO) mice and AAV9-mediated double knockdown (DKD) models.
- Employed EdU and pHH3 staining to assess cardiomyocyte proliferation.
- Conducted siRNA-mediated knockdown in neonatal rat ventricular myocyte (NRVM) cultures.
- Performed RNA sequencing (RNAseq) analysis on Btg1/2-depleted NRVMs.
Main Results:
- Btg1/2 DKO and DKD hearts showed increased mitotic cardiomyocytes at early postnatal stages (P7) but not in adulthood (P30/P14).
- Neonatal rat ventricular myocytes with Btg1/2 knockdown exhibited increased proliferation (EdU+) without affecting binucleation.
- RNAseq data indicated Btg1/2 regulate cell proliferation and reactive oxygen species (ROS) pathways.
Conclusions:
- Btg1 and Btg2 are novel contributing factors to the natural cardiomyocyte cell cycle arrest observed after birth in mammals.
- Btg1/2 function to inhibit neonatal cardiomyocyte proliferation and may modulate ROS pathways involved in cell cycle exit.
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