The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Identification and functional analysis of endothelial tip cell–enriched genes
Open accessAbstract
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.
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“Integrins, which regulate endothelial cell–cell and cell–matrix interactions, have been identified as alternative receptors for the angiopoietins in certain Tie2-negative non-endothelial cells22232425, and in the endothelial tip cells of angiogenic vessel sprouts, which express low levels of Tie2 (refs 26, 27).”
From Endothelial destabilization by angiopoietin-2 via integrin β1 activation (2015) · cites this paper as [26]
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Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., et al. (1997) · Science · doi:10.1126/science.277.5322.55 · Cited by 3,570
VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia
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Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor
Tatemoto, K., Hosoya, M., Habata, Y., Fujii, R., Kakegawa, T., Zou, M.-X., Kawamata, Y., Fukusumi, S., Hinuma, S., Kitada, C., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9489 · Cited by 1,684
Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system
Augustin, H. G., Koh, G. Y., Thurston, G., & Alitalo, K. K. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2639 · Cited by 1,512
multifunctional enzymes in cancer
Mohamed, M. M., & Sloane, B. F. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1949 · Cited by 1,303
uPAR: a versatile signalling orchestrator
Blasi, F., & Carmeliet, P. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm977 · Cited by 1,224
Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis
Noguera‐Troise, I., Daly, C., Papadopoulos, N. J., Coetzee, S., Boland, P., Gale, N. W., Lin, H. C., Yancopoulos, G. D., & Thurston, G. (2006) · Nature · doi:10.1038/nature05355 · Cited by 1,032
Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis
Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.-C., Chanthery, Y., Kowalski, J., Watts, R. J., Callahan, C., Kasman, I., et al. (2006) · Nature · doi:10.1038/nature05313 · Cited by 986
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Self-citationBlocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation
Tammela, T., Zarkada, G., Wallgard, E., Murtomäki, A., Suchting, S., Wirzenius, M., Waltari, M., Hellström, M., Schomber, T., Peltonen, R., et al. (2008) · Nature · doi:10.1038/nature07083 · Cited by 834
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Metadata
- Authors
- del Toro, R., Prahst, C., Mathivet, T., Siegfried, G., Kaminker, J. S., Larrivee, B., Breant, C., Duarte, A., Takakura, N., Fukamizu, A., Penninger, J., & Eichmann, A.
- Affiliations
- Inserm U833, Paris, France;
- Inserm (FR)
- Inserm U770, Kremlin Bicetre Hospital, Paris, France;
- Genentech (US)
- Centro Interdisciplinar de Investigaçao em Sanidade Animal, Faculdade de Medicina Veterinaria, Technical University of Lisbon, Lisbon, Portugal;
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- University of Tsukuba (JP)
- Institute of Molecular Biotechnology (AT)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-11-11
- Volume
- 116
- Issue
- 19
- Pages
- 4025-4033
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC4314527
- OpenAlex
- W2012483332
- Cited by
- 474
- References
- 48
- Citations by year
- 2026: 29 · 2025: 28 · 2024: 31 · 2023: 27 · 2022: 41 · 2021: 47 · 2020: 34 · 2019: 20 · 2018: 28 · 2017: 33 · 2016: 19 · 2015: 24 · 2014: 34 · 2013: 27 · 2012: 29
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Fondation Leducq
- Institut National de la Santé et de la Recherche Médicale
- Institut National Du Cancer
- Japan Society for the Promotion of Science (22248040)
- National Heart, Lung, and Blood Institute (R01HL111504)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- endothelial tip cells, DLL4, Notch signaling, retinal endothelial cells, angiogenesis, stalk cells, extracellular matrix degradation, basement membrane, secreted molecules, apelin, angiopoietin-2, matrix remodeling, zebrafish morpholino knockdown, knockout mice
- MeSH terms
- Apelin, Apelin Receptors, Animals, Calcium-Binding Proteins, Capillaries, Carrier Proteins, Extracellular Matrix, Multigene Family, Membrane Proteins, Mice, Inbred C57BL, Retinal Vessels, Zebrafish, Signal Transduction, Mice, Knockout, Neovascularization, Physiologic, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Intercellular Signaling Peptides and Proteins, Vascular Endothelial Growth Factor A, Endothelial Cells, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, Adipokines, Haploinsufficiency, TOR Serine-Threonine Kinases
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