First Author | Deckelbaum RA | Year | 2020 |
Journal | Angiogenesis | Volume | 23 |
Issue | 2 | Pages | 179-192 |
PubMed ID | 31754927 | Mgi Jnum | J:316219 |
Mgi Id | MGI:6834704 | Doi | 10.1007/s10456-019-09696-8 |
Citation | Deckelbaum RA, et al. (2020) The potassium channel Kcne3 is a VEGFA-inducible gene selectively expressed by vascular endothelial tip cells. Angiogenesis 23(2):179-192 |
abstractText | 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. |