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Transdifferentiation of hematopoietic stem cells and endothelial progenitors

Research Project

Project/Area Number 14207042
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKeio University

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)

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)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
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)
Keywordsanegiopoietin / 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
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).

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (40 results)

All 2005 2004 2003 2002 Other

All Journal Article (24 results) Publications (16 results)

  • [Journal Article] Angiopoietin-related growth factor antagonizes obesity and insulin resistance.2005

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Nat Med 11

      Pages: 400-408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-1 promotes LYVE-1 -positive lymphatic formation.2005

    • Author(s)
      Morisada T, et al.
    • Journal Title

      Blood Feb 10(Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-1 promotes lymphatic sprouting and hyperplasia.2005

    • Author(s)
      Tammela T, et al.
    • Journal Title

      Blood Mar 3(Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oncogenic transcription factor Evi-1 regulates hematopoietic stem cell proliferation through GATA-2 expression.2005

    • Author(s)
      Yuasa H, et al.
    • Journal Title

      EMBO J May 12(Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-1 promotes LYVE-1-positive lymphatic formation.2005

    • Author(s)
      Morisada T, et al.
    • Journal Title

      Blood, [Epub ahead of print]

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-1 promotes lymphatic sprouting and hyperplasia.2005

    • Author(s)
      Tammela T, et al.
    • Journal Title

      Blood, [Epub ahead of print]

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Oncogenic transcription factor Evi-1 regulates hematopoietic stem cell proliferation through GATA-2 expression.2005

    • Author(s)
      Yuasa H, et al.
    • Journal Title

      EMBO J, [Epub ahead of print]

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-related growth factor(AGF) antagonizes obesity and related insulin resistance.2005

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Nature Medicine (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiopoietin-1 promotes lymphatic hyperplasia.2005

    • Author(s)
      Tammela T, et al.
    • Journal Title

      Blood (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation.2005

    • Author(s)
      Morisada T, et al.
    • Journal Title

      Blood (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiopoietin-related growth factor (AGF) promotes angiogenesis.2004

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Blood 103

      Pages: 3760-3766

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells.2004

    • Author(s)
      Ito K, et al.
    • Journal Title

      Nature 431

      Pages: 997-1002

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Tie2/Angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche.2004

    • Author(s)
      Arai F, et al.
    • Journal Title

      Cell 118

      Pages: 149-161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of cell cycle in hematopoietic stem cells by the niche.2004

    • Author(s)
      Hirao A, et al.
    • Journal Title

      Cell Cycle 3

      Pages: 54-56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Tie2/Angiopoietin-1 signaling regulates Hematopoietic stem cell quiescence in the bone marrow niche.2004

    • Author(s)
      Arai F, et al.
    • Journal Title

      Cell 118

      Pages: 149-161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-related/Angiopoietin-like proteins regulate angiogenesis.2004

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Int J Hematol 80

      Pages: 21-28

    • NAID

      10013333855

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of oxidative stress by ATM is required for the self-renewal of hematopoietic stem cells.2004

    • Author(s)
      Ito K, et al.
    • Journal Title

      Nature 431

      Pages: 997-1002

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Tie2/Angiopoietin-1 signaling regulates quiescence of hematopoietic stem cells in a niche.2004

    • Author(s)
      Arai F, et al.
    • Journal Title

      Cell 118

      Pages: 149-161

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Angiopoietin-related growth factor(AGF) promotes angiogenesis.2004

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Blood 103

      Pages: 3760-3765

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification and characterization of stem cells in prepubertal spermatogogenesis in mice.2003

    • Author(s)
      Ohbo K, et al.
    • Journal Title

      Dev Biol 258

      Pages: 209-225

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration.2003

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Proc Natl Acad Sci USA 100

      Pages: 9494-9499

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of vasculogenesis and angiogenesis by EphB/ ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells.2002

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Blood 100

      Pages: 1326-1333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion molecule and participate in bone marrow formation.2002

    • Author(s)
      Arai F, et al.
    • Journal Title

      J Exp Med 195

      Pages: 1549-1563

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells.2002

    • Author(s)
      Oike Y, et al.
    • Journal Title

      Blood 100

      Pages: 1326-1333

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Oike Y, et al.: "Angiopoietin-related growth factor (AGF) promotes angiogenesis"Blood. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsunematsu R, et al.: "Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development."J.Biol.Chem.[Epub ahead of print]. DEC 12. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hamada K, et al.: "Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells."Arterioscler.Thromb.Vasc.Biol.. 23. 190-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Miyamoto T, et al.: "Differentiation and function of osteoclasts."The Keio Journal of Medicine. 52. 1-7 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada Y, et al.: "Neuropilin-1 on hematopoietic cells as a source of vascular development."Blood. 101. 1801-1809 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohbo K, et al.: "Identification and characterization of stem cells in prepubertal spermatogenesis in mice."Dev.Biol.. 258. 209-225 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oike Y, et al.: "Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling and regeneration."Proc.Natl.Acad.Sci.USA. 100. 9494-9499 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Li Z, et al.: "Defective smooth muscle development in qkI deficient mice."Dev.Growth Differ.. 45. 449-462 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito Y, et al.: "Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4."Cancer Res.. 63. 6651-6657 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maekawa H, et al.: "Ephrin-B2 induces migration of endothelial cells through the phosphatidylinositol-3 kinase pathway and promotes angiogenesis in adult vasculature."Arterioscler.Thromb.Vasc.Biol. 23. 190-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nosaka K, et al.: "Increased RANK ligand expression on adult T-cell leukemia cells is the critical factor of hyper-calcemia"Blood. 99. 634-640 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oike Y et al.: "Regulation of vasculogenesis and angiogenesis by Eph/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells"Blood. 100. 1326-1333 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arai F et al.: "Mesenchymal stem cells in perichondrium express activated cell adhesion molecule and participate in bone formation"J. Exp. Med. 195. 1449-1563 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suenobu S et al.: "A role of EphB4 receptor and its ligand, ephrin-B2 in erythropoiesis"Biochem Biophys Res Comm. 293. 1124-1131 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hamada K et al.: "Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells"Arterioscler Thromb Vasc Biol. 23(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ohbo K et al.: "Identification and characterization of stem cells in pre-pubertal spermatogenesis"Dev. Biol.. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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