Generation of specialized blood vessels via lymphatic transdifferentiation. 2022

Rudra N Das, and Yaara Tevet, and Stav Safriel, and Yanchao Han, and Noga Moshe, and Giuseppina Lambiase, and Ivan Bassi, and Julian Nicenboim, and Matthias Brückner, and Dana Hirsch, and Raya Eilam-Altstadter, and Wiebke Herzog, and Roi Avraham, and Kenneth D Poss, and Karina Yaniv
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel. rudra-nayan.das@weizmann.ac.il.

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.

UI MeSH Term Description Entries
D001808 Blood Vessels Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins). Blood Vessel,Vessel, Blood,Vessels, Blood
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015027 Zebrafish An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research. Brachydanio rerio,Danio rerio,B. rerio,D. rerio,Zebra Fish,Zebra Fishes,Zebra danio,Zebrafishes,D. rerios,Fishes, Zebra,Zebra danios,danio, Zebra
D042601 Lymphatic Vessels Tubular vessels that are involved in the transport of LYMPH and LYMPHOCYTES. Capillaries, Lymphatic,Lymphatic Capillaries,Lymphatic Venules,Venules, Lymphatic,Capillary, Lymphatic,Lymphatic Capillary,Lymphatic Venule,Lymphatic Vessel,Venule, Lymphatic,Vessel, Lymphatic,Vessels, Lymphatic
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D054338 Cell Transdifferentiation A naturally occurring phenomenon where terminally differentiated cells dedifferentiate to the point where they can switch CELL LINEAGES. The cells then differentiate into other cell types. Transdifferentiation, Cell,Cell Transdifferentiations,Transdifferentiations, Cell
D058500 Animal Fins Membranous appendage of fish and other aquatic organisms used for locomotion or balance. Animal Fin,Fin, Animal,Fins, Animal
D019070 Cell Lineage The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo. Cell Lineages,Lineage, Cell,Lineages, Cell

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