| Project/Area Number |
10307024
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
SUDA Toshio Institute of Molecular Embryology and Genetics, KUMAMOTO UNIVERSITY Professor, 発生医学研究センター, 教授 (60118453)
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| Co-Investigator(Kenkyū-buntansha) |
OIKE Yuichi Institute of Molecular Embryology and Genetics, KUMAMOTO UNIVERSITY, Assistant Professor, 発生医学研究センター, 助手 (90312321)
TAKAKURA Nobuyuki Institute of Molecular Embryology and Genetics, KUMAMOTO UNIVERSITY, Associate Professor, 発生医学研究センター, 助教授 (80291954)
山口 直人 熊本大学, 医学部, 助教授 (00166620)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥39,300,000 (Direct Cost: ¥39,300,000)
Fiscal Year 2000: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1999: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 1998: ¥25,100,000 (Direct Cost: ¥25,100,000)
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| Keywords | Microenvironment / Hemangioblast / Vitellin artery / Cell adhesion / Interaction between HSCs and ECs / Maintenance of stemness / Angiopoietin(Ang-1) / TIE2 receptor / 造血-血管内皮相互作用 / 末分化維持 / 一次造血 / AGM領域 / 二次造血 / 受容体型チロシンキナーゼTIE2 / Angiopoietin / インテグリン / 造血幹細胞 / 血管内皮細胞 / 造血支持組織 / 自己複製因子 / シグナルトラップ法 |
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| Research Abstract |
The association between hemopoietic stem cells (HSCs) and their microenvironment is central to the development and maintenance of a functional hematopoietic system.
We clarified following 4 points.
(1) We have investigated the function of TIE2 in the development of definitive hematopoiesis during embryogenesis. In vitellin artery, TIE2^+ hemopoietic cells aggregated and adhered to TIE2^+ endothelial cells (Immunity, 1998). Single TIE2^+ cells generated hematopoietic cells and endothelial cells(ECs) simultaneously. This TIE2^+ cells is identified as hemangioblasts(Blood, 1999).
(2) A TIE2-ligand, angiopoietin-1 (Ang-1) promoted the adhesion of TIE2^+ HSCs to fibronectin through integrins. This adhesion enhances not only the proliferation of hematopoietic progenitor cells but also the maintenance of stemness (Immunity, 1998).
(3) We found that Ang-1 derived from TIE2^+ HSCs promoted vessel sprouting into avascular areas (Cell, 2000). This suggests a close interaction between HSCs and ECs.
(4) IL-3-dependent BaF cells transfected constitutive active form of TIE2 receptor kinase represented long survival without IL-3. This indicates two possibilities ; one is the changes of cell cycle by adhesion and the other is the avoidance of apoptosis through TIE2 signaling. It is likely that hemopoietic stem cells forms their own microenvironment (Niche) by the adhesion to stromal cells or cell matrix.
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