Cell diversity and plasticity during atrioventricular heart valve EMTs.

Autor: Lotto J; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada.; Cell and Developmental Biology Program, University of British Columbia, Vancouver, BC, Canada., Cullum R; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada., Drissler S; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada.; Cell and Developmental Biology Program, University of British Columbia, Vancouver, BC, Canada., Arostegui M; Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada., Garside VC; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada.; Cell and Developmental Biology Program, University of British Columbia, Vancouver, BC, Canada.; Department of Anatomy and Physiology, University of Melbourne, Melbourne, VIC, Australia., Fuglerud BM; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Clement-Ranney M; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada., Thakur A; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada., Underhill TM; Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada., Hoodless PA; Terry Fox Laboratory, BC Cancer, Vancouver, BC, Canada. hoodless@bccrc.ca.; Cell and Developmental Biology Program, University of British Columbia, Vancouver, BC, Canada. hoodless@bccrc.ca.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada. hoodless@bccrc.ca.; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada. hoodless@bccrc.ca.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Sep 09; Vol. 14 (1), pp. 5567. Date of Electronic Publication: 2023 Sep 09.
DOI: 10.1038/s41467-023-41279-6
Abstrakt: 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.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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