| Project/Area Number |
14207042
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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 | Keio University |
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Principal Investigator |
OIKE Yuichi (2004) Keio University, Department of Medicine, Assistant professor, 医学部, 講師 (90312321)
須田 年生 (2002-2003) 慶應義塾大学, 医学部, 教授 (60118453)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAO Atsushi Keio University, Department of Medicine, Instructor, 医学部, 助手 (90343350)
OHBO Kazuyuki Keio University, Department of Medicine, Instructor, 医学部, 助手 (70250751)
尾池 雄一 慶應義塾大学, 医学部, 講師 (90312321)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥50,960,000 (Direct Cost: ¥39,200,000、Indirect Cost: ¥11,760,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2003: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2002: ¥35,360,000 (Direct Cost: ¥27,200,000、Indirect Cost: ¥8,160,000)
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| Keywords | anegiopoietin / Angptl / TIE2 / bone marrow / stem cell niche / osteoblast / angiogenesis / metabolism / 酸化ストレス / リンパ管新生 / ATM / 幹細胞分化転換 / 造血幹細胞 / 血管幹細胞 / AML1 / ES細胞 / Side Population / Hemangioblast / Tie2受容体 |
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| Research Abstract |
In this project, we try to clarify the differentiation pathway to hematopoietic stem cells (HSCs) and vascular endothelial cells from common progenitor cells or hemangioblasts. Hemogenic endothelial cells were defined in dorsal aorta in embryos, while hemangioblasts were not clarified yet at a clonal level in adult bone marrow. Both HSCs and endothelial cells express common surface molecules, CD31, CD34, Flk-1 and Tie2, which is a receptor for angiopoietins (Angs).
1)We have demonstrated that Tie2-positive HSCs adhere to Ang-1-producing osteoblasts, and that this signal is critical for maintaining the quiescent stem cells (Cell, 2004).
2)Angiopoietin-like proteins (Angptl) 1 and 2 synergistically show the anti-apoptotic effects on vascular endothelial cells using a Morpholino in Zebrafish.
3)Surprisingly, Angplt 6 is involved in the energy metabolism as well as angiogenesis. Angptl 6 KO mice show the obesity, while Tg mice show some resistance to obesity and diabetes (Nat.Med.2005).
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