Abstract P2003: Cardiomyocyte Polyploidy: Friend Or Foe?

Abstract

Developmental polyploidization (whole genome duplication) of cardiomyocytes is well conserved across mammals, birds and Drosophila . However, it is unclear whether precise control of cardiomyocyte polyploidy is essential. We found that there is a chamber-specific asymmetry to cardiomyocyte polyploidy in the Drosophila cardiac organ which is regulated by differential sensitivity of Insulin signaling. Higher ploidy cardiomyocytes correspond to the heart chamber, while lower ploidy cardiomyocytes correspond to the aorta chamber. Using immunofluorescence staining (IF), optical coherence tomography (OCT) and live imaging, we found that reducing chamber-specific ploidy affects cardiac function and reduces the velocity of circulating hemocytes, which indicates systemic heart failure. Intriguingly using human donor heart samples, we found that chamber specific asymmetry in cardiomyocyte ploidy and insulin sensitivity is similar to Drosophila . Our findings suggest that precise control of ploidy levels for cardiac organ sculpting is conserved across species. Polyploidization may have negative effects on cardiomyocyte regeneration, but our results suggest that region-specific control of ploidy levels is important for organ development and functionally.