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Angiogenesis
Published in: Angiogenesis 2/2020

Open Access 01-05-2020 | Original Paper

The potassium channel Kcne3 is a VEGFA-inducible gene selectively expressed by vascular endothelial tip cells

Authors: Ron A. Deckelbaum, Ivan B. Lobov, Eunice Cheung, Gabor Halasz, Saathyaki Rajamani, Julia Lerner, Chunxiang Tong, Zhe Li, Patricia Boland, Melissa Dominguez, Virginia Hughes, George D. Yancopoulos, Andrew J. Murphy, Gavin Thurston, Jingtai Cao, Carmelo Romano, Nicholas W. Gale

Published in: Angiogenesis | Issue 2/2020

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Abstract

Angiogenesis is largely driven by motile endothelial tip-cells capable of invading avascular tissue domains and enabling new vessel formation. Highly responsive to Vascular Endothelial Growth-Factor-A (VEGFA), endothelial tip-cells also suppress angiogenic sprouting in adjacent stalk cells, and thus have been a primary therapeutic focus in addressing neovascular pathologies. Surprisingly, however, there remains a paucity of specific endothelial tip-cell markers. Here, we employ transcriptional profiling and a lacZ reporter allele to identify Kcne3 as an early and selective endothelial tip-cell marker in multiple angiogenic contexts. In development, Kcne3 expression initiates during early phases of angiogenesis (E9) and remains specific to endothelial tip-cells, often adjacent to regions expressing VEGFA. Consistently, Kcne3 activation is highly responsive to exogenous VEGFA but maintains tip-cell specificity throughout normal retinal angiogenesis. We also demonstrate endothelial tip-cell selectivity of Kcne3 in several injury and tumor models. Together, our data show that Kcne3 is a unique marker of sprouting angiogenic tip-cells and offers new opportunities for investigating and targeting this cell type.
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Metadata
Title
The potassium channel Kcne3 is a VEGFA-inducible gene selectively expressed by vascular endothelial tip cells
Authors
Ron A. Deckelbaum
Ivan B. Lobov
Eunice Cheung
Gabor Halasz
Saathyaki Rajamani
Julia Lerner
Chunxiang Tong
Zhe Li
Patricia Boland
Melissa Dominguez
Virginia Hughes
George D. Yancopoulos
Andrew J. Murphy
Gavin Thurston
Jingtai Cao
Carmelo Romano
Nicholas W. Gale
Publication date
01-05-2020
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 2/2020
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-019-09696-8

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