Sara Munk Laursen - PhD Scholarship 2025
Project summary:
CORPLOIDIA - Cardiomyocyte polyploidy, an enigmatic challenge and a prospect for mammalian heart muscle cell renewal
The human heart lacks regenerative capacity because its muscle cells (cardiomyocytes) stop dividing shortly after birth. While polyploidy has long been seen as the main barrier to regeneration, this project investigates how cardiomyocytes first enter a dormant, non-dividing state during fetal development, before becoming polyploid. We hypothesize that this early dormancy, not polyploidy alone, blocks regeneration. CORPLOIDIA aims to define the molecular signals driving the transition from division to dormancy and polyploidy. By targeting these mechanisms, we aim to restore cardiomyocyte proliferation and enable heart tissue regeneration after injury.
Project Title
CORPLOIDIA - Cardiomyocyte polyploidy, an enigmatic challenge and a prospect for mammalian heart muscle cell renewal
Background
The adult heart cannot regenerate effectively after injury because cardiomyocytes (CMs) lose their ability to divide shortly after birth. While CM polyploidy has been viewed as the main barrier, new evidence suggests that an earlier state of “CM dormancy” may block division before polyploidy occurs. The timing and mechanisms behind this shift remain poorly understood.
Aim
CORPLOIDIA aims to uncover the molecular events driving the transition from dividing CMs to dormant and polyploid states. The goal is to determine whether CM dormancy can be reversed or manipulated, restoring the heart’s regenerative capacity after damage.
Methods
We will use a novel Rosa-Confetti mouse model combined with cell cycle, nucleation, and single-cell transcriptomic analyses to distinguish diploid from polyploid CMs and define their molecular states. This approach enables us to distinguish CM division from polyploidization and test strategies to either revert or induce dormancy and polyploidy. In the long term, these insights may support new regenerative therapies for heart disease.
Preliminary results
Previously published results from the group provide a transcriptomic map of developing cardiomyocytes. Identifying key transcription factors controlling the switch from division to polyploidy. Notably, ZEB1 was found to promote division before birth but induce polyploidy after, supporting the hypothesis that cardiomyocyte dormancy begins early and blocks regeneration independently of polyploidy: https://pubmed.ncbi.nlm.nih.gov/36862248/
Sara Munk Laursen
- MSc
- University of Southern Denmark, Clinical Institute
Main supervisor:
Professor Ditte Caroline Andersen, Klinisk Institut, University of Southern Denmark, and Forskningsenhed for Klinisk biokemi, Odense Universitetshospital (OUH)
Co-supervisors:
Professor Thomas Jespersen, University of Copenhagen, Institute of Biomedical Sciences
Ditte Gry Ellman, Ph.D, Associate Professor, Klinisk Institut, University of Southern Denmark, and Forskningsenhed for Klinisk biokemi, Odense Universitetshospital (OUH)