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Critical Role of the TIE2 Endothelial Cell Receptor in the Development of Definitive Hematopoiesis
Nobuyuki Takakura ,
Xu-Ling Huang ,
Takeshi Naruse ,
Isao Hamaguchi ,
Daniel J. Dumont ,
George D. Yancopoulos ,
Toshio Suda
November 1998
November 1998
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Abstract
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.