期刊
BLOOD
卷 116, 期 19, 页码 4025-4033出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-02-270819
关键词
-
类别
资金
- Inserm
- Agence Nationale de la Recherche (ANR Blanc)
- Institut National du Cancer
- Fondation Bettencourt
- Fondation Leducq
- Fondation pour la Recherche Medicale (FRM)
- Fundacion Marcelino Botin
- Association sur la Recherche contre le Cancer
- Deutsche Forschungsgemeinschaft
- Grants-in-Aid for Scientific Research [22248040] Funding Source: KAKEN
Sprouting of developing blood vessels is mediated by specialized motile endothelial cells localized at the tips of growing capillaries. Following behind the tip cells, endothelial stalk cells form the capillary lumen and proliferate. Expression of the Notch ligand Delta-like-4 (Dll4) in tip cells suppresses tip cell fate in neighboring stalk cells via Notch signaling. In DLL4(+/-) mouse mutants, most retinal endothelial cells display morphologic features of tip cells. We hypothesized that these mouse mutants could be used to isolate tip cells and so to determine their genetic repertoire. Using transcriptome analysis of retinal endothelial cells isolated from DLL4(+/-) and wild-type mice, we identified 3 clusters of tip cell-enriched genes, encoding extracellular matrix degrading enzymes, basement membrane components, and secreted molecules. Secreted molecules endothelial-specific molecule 1, angiopoietin 2, and apelin bind to cognate receptors on endothelial stalk cells. Knockout mice and zebrafish morpholino knockdown of apelin showed delayed angiogenesis and reduced proliferation of stalk cells expressing the apelin receptor APJ. Thus, tip cells may regulate angiogenesis via matrix remodeling, production of basement membrane, and release of secreted molecules, some of which regulate stalk cell behavior. (Blood. 2010;116(19):4025-4033)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据