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Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila

Archan Chakraborty, Nora G. Peterson, Juliet S. King, Ryan T. Gross, Michelle Mendiola Pla, Aatish Thennavan, Kevin C. Zhou, Sophia DeLuca, Nenad Bursac, Dawn E. Bowles, Matthew J. Wolf, View ORCID ProfileDonald T. Fox
doi: https://doi.org/10.1101/2023.02.10.528086
Archan Chakraborty
1Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA
2Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USA
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Nora G. Peterson
1Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA
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Juliet S. King
1Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA
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Ryan T. Gross
3Department of Surgery, Duke University, Durham, NC 27710, USA
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Michelle Mendiola Pla
3Department of Surgery, Duke University, Durham, NC 27710, USA
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Aatish Thennavan
4Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX, USA
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Kevin C. Zhou
5Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA
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Sophia DeLuca
6Department of Biomedical Engineering, Duke University, Durham, NC, USA
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Nenad Bursac
2Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USA
6Department of Biomedical Engineering, Duke University, Durham, NC, USA
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Dawn E. Bowles
3Department of Surgery, Duke University, Durham, NC 27710, USA
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Matthew J. Wolf
7Department of Medicine, University of Virginia, Charlottesville, VA, USA
8Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, USA
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Donald T. Fox
1Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA
2Duke Regeneration Center, Duke University School of Medicine, Durham, NC, USA
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  • ORCID record for Donald T. Fox
  • For correspondence: don.fox@duke.edu
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SUMMARY

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 Statement

The authors have declared no competing interest.

Footnotes

  • Conceptualization: A.C., N.G.P D.T.F.; Methodology: A.C.; N.G.P, J.K., S.D., M.W. Validation: A.C., N.G.P, J.K., M.W., D.T.F; Formal Analysis: A.C., N.G.P., J.K., D.T.F.; Investigation: A.C., N.G.P., J.K., R.G., M.M.P, A.T., K.C.Z., S.D. M.W.; Data curation: A.C.; Writing: A.C., D.T.F.; Visualization: A.C.; N.G.P, J.K.; M.W. Supervision: M.W., D.T.F.; Funding acquisition: A.C., N.G.P, S.D., N.B., M.W., D.T.F.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 12, 2023.
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Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila
Archan Chakraborty, Nora G. Peterson, Juliet S. King, Ryan T. Gross, Michelle Mendiola Pla, Aatish Thennavan, Kevin C. Zhou, Sophia DeLuca, Nenad Bursac, Dawn E. Bowles, Matthew J. Wolf, Donald T. Fox
bioRxiv 2023.02.10.528086; doi: https://doi.org/10.1101/2023.02.10.528086
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Conserved Chamber-Specific Polyploidy Maintains Heart Function in Drosophila
Archan Chakraborty, Nora G. Peterson, Juliet S. King, Ryan T. Gross, Michelle Mendiola Pla, Aatish Thennavan, Kevin C. Zhou, Sophia DeLuca, Nenad Bursac, Dawn E. Bowles, Matthew J. Wolf, Donald T. Fox
bioRxiv 2023.02.10.528086; doi: https://doi.org/10.1101/2023.02.10.528086

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