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Updated: Feb 13, 2026
Visualization of Cell Cycle Variations and Determination of Nucleation in Postnatal Cardiomyocytes
Published on: February 24, 2017
Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration
Tamer M A Mohamed1, Yen-Sin Ang2, Ethan Radzinsky2
1Gladstone Institute of Cardiovascular Disease and Roddenberry Stem Cell Center, San Francisco, CA 94158, USA; Institute of Cardiovascular Sciences, University of Manchester, Manchester M13 9PT, UK; Faculty of Pharmacy, Zagazig University, Al Sharqia Governorate, Egypt; Tenaya Therapeutics, South San Francisco, CA 94080, USA.
Abstract:
Human diseases are often caused by loss of somatic cells that are incapable of re-entering the cell cycle for regenerative repair. Here, we report a combination of cell-cycle regulators that induce stable cytokinesis in adult post-mitotic cells. We screened cell-cycle regulators expressed in proliferating fetal cardiomyocytes and found that overexpression of cyclin-dependent kinase 1 (CDK1), CDK4, cyclin B1, and cyclin D1 efficiently induced cell division in post-mitotic mouse, rat, and human cardiomyocytes. Overexpression of the cell-cycle regulators was self-limiting through proteasome-mediated degradation of the protein products. In vivo lineage tracing revealed that 15%-20% of adult cardiomyocytes expressing the four factors underwent stable cell division, with significant improvement in cardiac function after acute or subacute myocardial infarction. Chemical inhibition of Tgf-β and Wee1 made CDK1 and cyclin B dispensable. These findings reveal a discrete combination of genes that can efficiently unlock the proliferative potential in cells that have terminally exited the cell cycle.
Insights
Scientists identified four cell-cycle regulators that trigger cell division in adult cardiomyocytes, promoting heart repair after injury. This breakthrough unlocks regenerative potential in cells previously unable to divide.
Area of Science:
- Cardiovascular Biology
- Cellular Regeneration
- Molecular Medicine
Background:
- Human diseases often stem from the loss of somatic cells unable to regenerate.
- Post-mitotic cells, like adult cardiomyocytes, typically cannot divide for repair.
Purpose of the Study:
- To identify a combination of cell-cycle regulators capable of inducing stable cell division in adult post-mitotic cells.
- To explore the potential for regenerative repair in the adult heart.
Main Methods:
- Screened cell-cycle regulators from proliferating fetal cardiomyocytes.
- Overexpressed specific regulators (CDK1, CDK4, cyclin B1, cyclin D1) in adult mouse, rat, and human cardiomyocytes.
- Utilized in vivo lineage tracing and assessed cardiac function post-myocardial infarction.
Main Results:
- Overexpression of CDK1, CDK4, cyclin B1, and cyclin D1 induced stable cell division in 15%-20% of adult cardiomyocytes.
- The induced cell division led to significant functional improvement after myocardial infarction.
- Proteasome-mediated degradation limited the overexpression of these regulators.
- Inhibition of Tgf-β and Wee1 rendered CDK1 and cyclin B dispensable.
Conclusions:
- A specific combination of cell-cycle regulators can unlock the proliferative capacity of terminally differentiated cells.
- This approach offers a novel strategy for cardiac regeneration and treating heart diseases caused by cell loss.
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