Generation of specialized blood vessels via lymphatic transdifferentiation.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Das, RN; Tevet, Y; Safriel, S; Han, Y; Moshe, N; Lambiase, G; Bassi, I; Nicenboim, J; Brückner, M; Hirsch, D; Eilam-Altstadter, R; Herzog, W; Avraham, R; Poss, KD; Yaniv, K

Published Date

  • June 2022

Published In

Volume / Issue

  • 606 / 7914

Start / End Page

  • 570 - 575

PubMed ID

  • 35614218

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/s41586-022-04766-2

Language

  • eng

Conference Location

  • England