Generation of specialized blood vessels via lymphatic transdifferentiation

Rudra N. Das (), Yaara Tevet, Stav Safriel, Yanchao Han, Noga Moshe, Giuseppina Lambiase, Ivan Bassi, Julian Nicenboim, Matthias Brückner, Dana Hirsch, Raya Eilam-Altstadter, Wiebke Herzog, Roi Avraham, Kenneth D. Poss and Karina Yaniv ()
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Rudra N. Das: Weizmann Institute of Science
Yaara Tevet: Weizmann Institute of Science
Stav Safriel: Weizmann Institute of Science
Yanchao Han: Duke University School of Medicine
Noga Moshe: Weizmann Institute of Science
Giuseppina Lambiase: Weizmann Institute of Science
Ivan Bassi: Weizmann Institute of Science
Julian Nicenboim: Weizmann Institute of Science
Matthias Brückner: Max Plank Institute for Molecular Biomedicine
Dana Hirsch: Weizmann Institute of Science
Raya Eilam-Altstadter: Weizmann Institute of Science
Wiebke Herzog: Max Plank Institute for Molecular Biomedicine
Roi Avraham: Weizmann Institute of Science
Kenneth D. Poss: Duke University School of Medicine
Karina Yaniv: Weizmann Institute of Science

Nature, 2022, vol. 606, issue 7914, 570-575

Abstract: Abstract The lineage and developmental trajectory of a cell are key determinants of cellular identity. In the vascular system, endothelial cells (ECs) of blood and lymphatic vessels differentiate and specialize to cater to the unique physiological demands of each organ1,2. Although lymphatic vessels were shown to derive from multiple cellular origins, lymphatic ECs (LECs) are not known to generate other cell types3,4. Here we use recurrent imaging and lineage-tracing of ECs in zebrafish anal fins, from early development to adulthood, to uncover a mechanism of specialized blood vessel formation through the transdifferentiation of LECs. Moreover, we demonstrate that deriving anal-fin vessels from lymphatic versus blood ECs results in functional differences in the adult organism, uncovering a link between cell ontogeny and functionality. We further use single-cell RNA-sequencing analysis to characterize the different cellular populations and transition states involved in the transdifferentiation process. Finally, we show that, similar to normal development, the vasculature is rederived from lymphatics during anal-fin regeneration, demonstrating that LECs in adult fish retain both potency and plasticity for generating blood ECs. Overall, our research highlights an innate mechanism of blood vessel formation through LEC transdifferentiation, and provides in vivo evidence for a link between cell ontogeny and functionality in ECs.

Date: 2022
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DOI: 10.1038/s41586-022-04766-2

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