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To be or not to be: endothelial cell plasticity in development, repair, and disease

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Abstract

Endothelial cells display an extraordinary plasticity both during development and throughout adult life. During early development, endothelial cells assume arterial, venous, or lymphatic identity, while selected endothelial cells undergo additional fate changes to become hematopoietic progenitor, cardiac valve, and other cell types. Adult endothelial cells are some of the longest-lived cells in the body and their participation as stable components of the vascular wall is critical for the proper function of both the circulatory and lymphatic systems, yet these cells also display a remarkable capacity to undergo changes in their differentiated identity during injury, disease, and even normal physiological changes in the vasculature. Here, we discuss how endothelial cells become specified during development as arterial, venous, or lymphatic endothelial cells or convert into hematopoietic stem and progenitor cells or cardiac valve cells. We compare findings from in vitro and in vivo studies with a focus on the zebrafish as a valuable model for exploring the signaling pathways and environmental cues that drive these transitions. We also discuss how endothelial plasticity can aid in revascularization and repair of tissue after damage- but may have detrimental consequences under disease conditions. By better understanding endothelial plasticity and the mechanisms underlying endothelial fate transitions, we can begin to explore new therapeutic avenues.

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Acknowledgements

The authors thank members of the Weinstein lab for their help and support. We apologize to authors whose work we could not cite due to space limitations.

Funding

This paper was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (ZIA-HD008915, ZIA-HD008808, and ZIA-HD001011, to BMW).

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  1. Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Leah J. Greenspan & Brant M. Weinstein

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  1. Leah J. Greenspan
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Greenspan, L.J., Weinstein, B.M. To be or not to be: endothelial cell plasticity in development, repair, and disease. Angiogenesis 24, 251–269 (2021). https://doi.org/10.1007/s10456-020-09761-7

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