| Project/Area Number |
08457279
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
SUDA Toshio Kumamoto University School of Medicine, Professor, 医学部, 教授 (60118453)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAKURA Nobuyuki Kumamoto University School of Medicine, Research Associate, 医学部, 助手 (80291954)
YAMAGUCHI Yuji Kumamoto UniversitySchool of Medicine, Assistant Professor (00220286)
YAMAGUCHI Naoto Kumamoto University School of Medicine, Associate Professor (00166620)
IWAMA Atsushi Kumamoto University School of Medicine, Research Associate (70244126)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥4,400,000 (Direct Cost: ¥4,400,000)
|
|---|
| Keywords | AGM region / Hemangioblast / Angiopoietin / TEK / 血液幹細胞 / 血管内皮細胞 / TIE / アンギオポエチレン |
|---|
| Research Abstract |
Association between hematopoietic stem cells and their microenvironment are central to the development and maintenance of a functional hematopoietic system. The TEK receptor tyrosine kinase and its ligands angiopoietin-1 and -2 have been documented to be involved in the formation of the embryonic vasculature. Although the defect of vasuculo-angiogenesis was confirmed in both knockout mice of TEK and angiopoietin-1, the precise function of these molecules has not been well understood. Here, we evaluated the expression and function of TEK during embryogenesis, especially in the AGM (aorta-gonad-mesonephros) region, omphalo-mesenteric artery and vitelline artery, where definitive hematopoiesis newly takes place. In the vitelline artery at E9.5, TEK^+ hematopoietic cells aggregated each other and adhered to TEK^+ endothelial cells. Definitive hematopoiesis was not detected in TEK-deficient embryo. Soluble TEK protein inhibited the development of hematopoiesis and angiogenesis in AGM explant culture, and TEK knockout mice showed severely impaired definitive hematopoiesis. In vitro study, we found a novel function of angiopoietin-1 and -2 which promote expressing TEK cells to adhere to fibronectin and to aggregate each other. Finally, we showed that supplement of VEGF in the presence of angiopoietins promoted the proliferation of both hematopoietic cells and endothelial cells. These data provide a new regulatory system of the development and maintenance of definitive hematopoiesis through interaction with microenvironment.
|
