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Isolation and Profiling of Human Primary Mesenteric Arterial Endothelial Cells at the Transcriptome Level
Published on: March 14, 2022
Identification and functional analysis of endothelial tip cell-enriched genes
Raquel del Toro1, Claudia Prahst, Thomas Mathivet
1Inserm U833, Paris, France.
Blood
|August 14, 2010
Summary
Tip cells guide new blood vessel growth. Researchers identified genes in tip cells that regulate stalk cell behavior and blood vessel formation, revealing new therapeutic targets for angiogenesis.
Area of Science:
- Vascular biology
- Endothelial cell biology
- Molecular genetics
Background:
- Blood vessel sprouting involves tip and stalk endothelial cells.
- Notch signaling, mediated by Delta-like-4 (Dll4), distinguishes tip cells from stalk cells.
- DLL4(+/-) mice exhibit an enrichment of tip cell phenotypes.
Purpose of the Study:
- To identify genes enriched in tip cells using DLL4(+/-) mouse mutants.
- To elucidate the role of tip cell-derived molecules in regulating angiogenesis.
Main Methods:
- Transcriptome analysis of retinal endothelial cells from DLL4(+/-) and wild-type mice.
- Gene expression profiling to identify tip cell-enriched gene clusters.
- Functional studies using knockout mice and zebrafish morpholino knockdown of apelin.
Main Results:
- Three clusters of tip cell-enriched genes were identified: matrix-degrading enzymes, basement membrane components, and secreted molecules.
- Secreted molecules like angiopoietin 2 and apelin were found to act on endothelial stalk cells.
- Apelin signaling is crucial for stalk cell proliferation and angiogenesis, as demonstrated by knockout and knockdown studies.
Conclusions:
- Tip cells regulate angiogenesis through matrix remodeling, basement membrane production, and secretion of signaling molecules.
- Tip cell-derived secreted factors, such as apelin, directly influence stalk cell behavior and proliferation.
- These findings offer insights into the molecular mechanisms controlling blood vessel formation and potential therapeutic strategies for angiogenesis-related disorders.
