PMID:16219799

Citation	Hamaguchi, I, Morisada, T, Azuma, M, Murakami, K, Kuramitsu, M, Mizukami, T, Ohbo, K, Yamaguchi, K, Oike, Y, Dumont, DJ and Suda, T (2006) Loss of Tie2 receptor compromises embryonic stem cell-derived endothelial but not hematopoietic cell survival. Blood 107:1207-13
Abstract	Tie2 is a receptor-type tyrosine kinase expressed on hematopoietic stem cells and endothelial cells. We used cultured embryonic stem (ES) cells to determine the function of Tie2 during early vascular development and hematopoiesis. Upon differentiation, the ES cell-derived Tie2+ Flk1+ fraction was enriched for hematopoietic and endothelial progenitor cells. To investigate lymphatic differentiation, we used a monoclonal antibody against LYVE-1 and found that LYVE-1+ cells derived from Tie2+ Flk1+ cells possessed various characteristics of lymphatic endothelial cells. To determine whether Tie2 played a role in this process, we analyzed differentiation of Tie2-/- ES cells. Although the initial numbers of LYVE-1+ and PECAM-1+ cells derived from Tie2-/- cells did not vary significantly, the number of both decreased dramatically upon extended culturing. Such decreases were rescued by treatment with a caspase inhibitor, suggesting that reductions were due to apoptosis as a consequence of a lack of Tie2 signaling. Interestingly, Tie2-/- ES cells did not show measurable defects in development of the hematopoietic system, suggesting that Tie2 is not essential for hematopoietic cell development.
Links	PubMed PMC1895914 Online version:10.1182/blood-2005-05-1823
Keywords	Animals; Antigens, CD31/metabolism; Cell Differentiation/physiology; Cell Survival/physiology; Cells, Cultured; Embryo, Mammalian/cytology; Embryo, Mammalian/physiology; Endothelial Cells/cytology; Endothelial Cells/physiology; Glycoproteins/metabolism; Hematopoiesis/physiology; Hematopoietic Stem Cells/cytology; Hematopoietic Stem Cells/physiology; Mice; Neovascularization, Physiologic/physiology; Receptor, TIE-2/metabolism; Signal Transduction/physiology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:VGFR2		GO:0010468 : regulation of gene expression	ECO:0000315:		P		Fig.1	complete
MOUSE:TIE2	incorrect (CACAO)	GO:0007507 : heart development	ECO:0000304:		P		intro 'Tie2-deficient mice exhibit severe defects in vascular and heart development and die by E9.5'	complete
MOUSE:TIE2	incorrect (CACAO)	GO:0035162 : embryonic hemopoiesis	ECO:0000304:		P		intro 'Tie2 is dispensable for embryonic hematopoiesis using ES cell mouse chimeras'	complete
MOUSE:TIE2	NOT	GO:0060218 : hemopoietic stem cell differentiation	ECO:0000315:		P		Fig.3A-D; Fig.4G	complete
MOUSE:TIE2		GO:0060837 : blood vessel endothelial cell differentiation	ECO:0000315:		P		Fig.4	complete
MOUSE:TIE2		GO:0060836 : lymphatic endothelial cell differentiation	ECO:0000315:		P		Fig.4	complete
MOUSE:TIE2		GO:0006916 : anti-apoptosis	ECO:0000315:		P		Fig.5	complete
MOUSE:TIE2		GO:0010468 : regulation of gene expression	ECO:0000315:		P		Fig.1	complete

References

See Help:References for how to manage references in GONUTS.