PT  - JOURNAL ARTICLE
AU  - Archan Chakraborty
AU  - Nora G. Peterson
AU  - Juliet S. King
AU  - Ryan T. Gross
AU  - Michelle Mendiola Pla
AU  - Aatish Thennavan
AU  - Kevin C. Zhou
AU  - Sophia DeLuca
AU  - Nenad Bursac
AU  - Dawn E. Bowles
AU  - Matthew J. Wolf
AU  - Donald T. Fox
TI  - Conserved Chamber-Specific Polyploidy Maintains Heart Function in <em>Drosophila</em>
AID  - 10.1101/2023.02.10.528086
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.02.10.528086
4099  - http://biorxiv.org/content/early/2023/02/12/2023.02.10.528086.short
4100  - http://biorxiv.org/content/early/2023/02/12/2023.02.10.528086.full
AB  - Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conserved asymmetry in polyploidy level between cardiac chambers in Drosophila larvae and humans. In Drosophila, differential Insulin Receptor (InR) sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume, cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic systemic human heart failure. Using human donor hearts, we reveal asymmetry in nuclear volume (ploidy) and insulin signaling between the left ventricle and atrium. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery.Competing Interest StatementThe authors have declared no competing interest.