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Cell diversity and plasticity during atrioventricular heart valve EMTs

Author

Listed:
  • Jeremy Lotto

    (BC Cancer
    University of British Columbia)

  • Rebecca Cullum

    (BC Cancer)

  • Sibyl Drissler

    (BC Cancer
    University of British Columbia)

  • Martin Arostegui

    (University of British Columbia
    University of British Columbia)

  • Victoria C. Garside

    (BC Cancer
    University of British Columbia
    University of Melbourne)

  • Bettina M. Fuglerud

    (BC Cancer
    University of British Columbia)

  • Makenna Clement-Ranney

    (BC Cancer)

  • Avinash Thakur

    (BC Cancer
    University of British Columbia)

  • T. Michael Underhill

    (University of British Columbia
    University of British Columbia
    University of British Columbia)

  • Pamela A. Hoodless

    (BC Cancer
    University of British Columbia
    University of British Columbia
    University of British Columbia)

Abstract

Epithelial-to-mesenchymal transitions (EMTs) of both endocardium and epicardium guide atrioventricular heart valve formation, but the cellular complexity and small scale of this tissue have restricted analyses. To circumvent these issues, we analyzed over 50,000 murine single-cell transcriptomes from embryonic day (E)7.75 hearts to E12.5 atrioventricular canals. We delineate mesenchymal and endocardial bifurcation during endocardial EMT, identify a distinct, transdifferentiating epicardial population during epicardial EMT, and reveal the activation of epithelial-mesenchymal plasticity during both processes. In Sox9-deficient valves, we observe increased epithelial-mesenchymal plasticity, indicating a role for SOX9 in promoting endothelial and mesenchymal cell fate decisions. Lastly, we deconvolve cell interactions guiding the initiation and progression of cardiac valve EMTs. Overall, these data reveal mechanisms of emergence of mesenchyme from endocardium or epicardium at single-cell resolution and will serve as an atlas of EMT initiation and progression with broad implications in regenerative medicine and cancer biology.

Suggested Citation

  • Jeremy Lotto & Rebecca Cullum & Sibyl Drissler & Martin Arostegui & Victoria C. Garside & Bettina M. Fuglerud & Makenna Clement-Ranney & Avinash Thakur & T. Michael Underhill & Pamela A. Hoodless, 2023. "Cell diversity and plasticity during atrioventricular heart valve EMTs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41279-6
    DOI: 10.1038/s41467-023-41279-6
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