4.6 Review

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

Journal

ANGIOGENESIS
Volume 24, Issue 2, Pages 251-269

Publisher

SPRINGER
DOI: 10.1007/s10456-020-09761-7

Keywords

Endothelial cell; Vascular plasticity; Transdifferentiation; Zebrafish

Funding

  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [ZIA-HD008915, ZIA-HD008808, ZIA-HD001011]

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Endothelial cells exhibit remarkable plasticity during development and adulthood, capable of transforming into different cell types. While crucial for the proper function of circulatory and lymphatic systems, they also display adaptability in response to injury, disease, and physiological changes in vasculature. Understanding endothelial plasticity and fate transitions may lead to new therapeutic approaches.
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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