In vitro hematopoietic and endothelial cell development from cells expressing TEK receptor in murine aorta-gonad-mesonephros region

被引:66
作者
Hamaguchi, I
Huang, XL
Takakura, N
Tada, J
Yamaguchi, Y
Kodama, H
Suda, T
机构
[1] Kumamoto Univ, Sch Med, Dept Cell Differentiat, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan
[2] Bayer Yakuhin Ltd, Res Ctr Kyoto, Kyoto, Japan
关键词
D O I
10.1182/blood.V93.5.1549.405k25_1549_1556
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies have shown that long-term repopulating hematopoietic stem cells (HSCs) first appear in the aorta-gonad-mesonephros (AGM) region. Our immunohistochemistry study showed that TEK+ cells existed in the AGM region. Approximately 5% of AGM cells were TEK+, and most of these were CD34(+) and c-Kit(+). We then established a coculture system of AGM cells using a stromal cell line, OP9, which is deficient in macrophage colony-stimulating factor (M-CSF). With this system, we showed that AGM cells at 10.5 days postcoitum (dpc) differentiated and proliferated into both hematopoietic and endothelial cells. Proliferating hematopoietic cells contained a significant number of colony-forming cells in culture (CFU-C) and in spleen (CFU-S). Among primary AGM cells at 10.5 dpc, sorted TEK+ AGM cells generated hematopoietic cells and platelet endothelial cell adhesion molecule (PECAM)-1(+) endothelial cells on the OP9 stromal layer, while TEK- cells did not. When a ligand for TEK, angiopoietin-1, was added to the single-cell culture of AGM, endothelial cell growth was detected in the wells where hematopoietic colonies grew. Although the incidence was still low (1/135), we showed that single TEK+ cells generated hematopoietic cells and endothelial cells simultaneously, using a single-cell deposition system. This in vitro coculture system shows that the TEK+ fraction of primary AGM cells is a candidate for hemangioblasts, which can differentiate into both hematopoietic cells and endothelial cells. (C) 1999 by The American Society of Hematology.
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页码:1549 / 1556
页数:8
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