Upon injury of the adult mammalian heart, cardiomyocytes are lost and are never replaced, which is attributed to the combined lack of resident cardiac stem cells and roadblocks that prevent pre-existing cardiomyocytes to re-enter the cell cycle. In the adult zebrafish heart however, the injured heart muscle is efficiently replaced due to cardiomyocyte turnover. A central question in the heart regeneration field is why the regenerative capacity is very low in mammals, but it is very efficient in other species like zebrafish. To address this question my group is using TOMO-seq, a method for spatially-resolved transcriptomics, and single-cell RNA-sequencing to discover new mechanisms that drive cardiomyocyte proliferation. In this seminar I will present our findings implicating metabolic reprogramming of cardiomyocytes as a driver for cardiomyocyte proliferation. In addition, I will discuss the role of epicardial-derived fibroblasts in regulating scar formation and cardiomyocyte proliferation.
Jeroen Bakkers is group leader at the Hubrecht Institute and professor of Molecular Cardiogenetics at the University Medical Center Utrecht. His group uses the zebrafish (Danio rerio) as a model system to study various processes. The research lines of the Bakkers group include unravelling the genetics of normal cardiac development and body axis formation during development, investigating the molecular mechanisms of heart regeneration in the zebrafish and how this can be compared to heart injury in the mammals, and modelling of human (cardiac) disease in the zebrafish to unravel biological mechanisms behind the disease and to identify new drug targets.