RT Journal Article
SR Electronic
T1 Conserved Chamber-Specific Polyploidy Maintains Heart Function in <em>Drosophila</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.10.528086
DO 10.1101/2023.02.10.528086
A1 Archan Chakraborty
A1 Nora G. Peterson
A1 Juliet S. King
A1 Ryan T. Gross
A1 Michelle Mendiola Pla
A1 Aatish Thennavan
A1 Kevin C. Zhou
A1 Sophia DeLuca
A1 Nenad Bursac
A1 Dawn E. Bowles
A1 Matthew J. Wolf
A1 Donald T. Fox
YR 2023
UL http://biorxiv.org/content/early/2023/02/12/2023.02.10.528086.abstract
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.