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Publication : Cell diversity and plasticity during atrioventricular heart valve EMTs.

First Author  Lotto J Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  5567
PubMed ID  37689753 Mgi Jnum  J:340446
Mgi Id  MGI:7527925 Doi  10.1038/s41467-023-41279-6
Citation  Lotto J, et al. (2023) Cell diversity and plasticity during atrioventricular heart valve EMTs. Nat Commun 14(1):5567
abstractText  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.
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