Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis.
We have investigated the function of TIE2/TEK receptor tyrosine kinase in the development of definitive hematopoiesis. In the vitelline artery at 9.5 days postcoitum (d.p.c.), TIE2+ hematopoietic cells aggregated and adhered to TIE2+ endothelial cells. Soluble TIE2-Fc chimeric protein inhibited the development of hematopoiesis and angiogenesis in the para-aortic splanchnopleural mesoderm (P-Sp) explant culture, and TIE2-deficient mice showed severely impaired definitive hematopoiesis. An in vitro study revealed that Angiopoietin-1 but not Angiopoietin-2 promoted the adhesion to fibronectin (FN) through integrins in TIE2-transfected cells and primary TIE2+ cells sorted from 9.5 d.p.c. P-Sp. Adhesion of TIE2+ cells induced by Angiopoietin-1 enhanced the proliferation of hematopoietic progenitor cells.
Takakura
Nobuyuki
N
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Japan.
Huang
Xu-Ling
XL
Naruse
Takeshi
T
Hamaguchi
Isao
I
Dumont
Daniel J
DJ
Yancopoulos
George D
GD
Suda
Toshio
T
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000648:ultrastructure*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology / Q000502:physiology; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000494:pharmacology / Q000502:physiology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D042787:Receptor, TIE-2; D015398:Signal Transduction / Q000502:physiology
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D005353:Fibronectins; D008562:Membrane Glycoproteins; D011506:Proteins; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2