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immunity.com
Critical Role of the TIE2 Endothelial Cell Receptor in the Development of Definitive Hematopoiesis
Nobuyuki Takakura1, Xu-Ling Huang1, Takeshi Naruse1, Isao Hamaguchi1, Daniel J. Dumont2, George D. Yancopoulos3, Toshio Suda1
1 Department of Cell Differentiation, Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
2 Division of Cancer Biology, Sunnybrook and Women's College Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5
3 Regeneron Pharmaceuticals, Incorporated, 777 Old Saw Mill River Road, Tarrytown, New York 10591
Corresponding author: Toshio Suda, 81 96 373 5328 (phone), 81 96 373 5332 (fax), sudato@gpo.kumamoto-u.ac.jp.
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.
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