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Functional analyzes for common receptor tyrosine kinases of hematopoietic stem cells and vascular endothelial cells

Research Project

Project/Area Number 08457279
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKumamoto 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)
KeywordsAGM 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.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Hashiyama M: "Predominant expression of a receptor tyrosine kinase,TIE inhematopoietic progenitor cells and B cell line." Blood. 87. 93-101 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakano S: "Characterization of a ligand for receptor protein-tyrosine kinase HTKexpressed in immature hematopoietic cells." Oncogene. 13. 813-822 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iwama A: "STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional dockingsite conserved among HGF receptor family." EMBOJ. 15. 5866-5876 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakamoto O: "Role of macrophage-stimulating protein and its receptor,RON tyrosine kinase in ciliary motility." J Clin Invest. 99. 701-709 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirao A: "Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36-anchored Lyn tyrosine in thrombin-stimulated platelets." EMBOJ. 16. 2342-2351 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inada T: "Selective expression of the receptor tyrosine kinase,HTK on human erythroid progenitor cells." Blood. 89. 2757-2765 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yano M: "Expression and function of murine receptor tyrosine kinases,TIE and TEK in hemtopoietic stem cells." Blood. 89. 4317-4326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takakura N: "PDGFα expressing during mouse embryogenesis : Immunolocalization analyzed by whole-mount immunohistostaining using the monoclonal anti-mouse-PDGFRα antibody APA" J Histochem Cytochem. 45. 883-893 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakano S: "Bone Marrow Transplantation" Springer, 331 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato A: "Leukocyte Typing VI" Garland Publishing Inc., 1342 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hashiyama M et al :"Predominant expression of a receptor tyrosine kinase, TIE in hematopoietic progenitor cells and B cell line." Blood. 87. 93-101 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakano S et al :"Characterization of a ligand for receptor protein-tyrosine kinase HTK expressed in immature hematopoietic cells." Oncogene. 13. 813-822 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Iwama A et al :"STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among HGF receptor family." EMBO J. 15. 5866-5876 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakamoto O et al :"Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase in ciliary motility." J Clin Invest. 99. 701-709 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hirao A et al :"Translocation of the Csk homologous kinase (Chk/Hyl) regulates CD36-anchored Src-family kinases in platelet activation." EMBO J. 16. 2342-2351 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Inada T et al :"Selective expression of the receptor tyrosine kinase, HTK on human erythroid progenitor cells." Blood. 89. 2757-2765 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yano M et al :"Expression and function of murine receptor tyrosine kinases, TIE and TEK in hematopoietic stem cells." Blood. 89. 4317-4326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takakura N et al :"PDGFa expressing during mouse embryogenesis : Immunolocalization analyzed by whole-mount immunohistostaning using the monoclonal anti-mouse-PDGFRalpha antibody APA5." J Histochem Cytochem. 45. 883-893 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sakano S et al :: Identification and characterization of a ligand for receptor protein-tyrosine kinase HTK expressed in hematopoietic cells. "Bone marrow transplantation" (eds Ikehara S,Takaku F,Good RA). Springer, Tokyo, 36-46 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato A et al :: Cytokine Receptor expression : Expression of receptor tyrosine kinases, c-Kit, Tie and Htk in hematopoietic progenitor cells. "Leukocyte Typing VI"(Kishimoto T et al eds). Garland Publishing Inc.New York and London, 911-913 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takakura N.: "PDGFα expressing during mouse embryogenesis : Immunolocalization analyzed by wholemount immunohistostaining using the monoclonal anti-mouse-PDGFRα antibody APA5." J Histochem Cytochem. 45. 883-893 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yano M.: "Expression and function of murine receptor tyrosine kinases, TIE and TEK in hemtopoietic stem cells." Blood. 89. 4317-4326 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Inada T.: "Selective expression of the receptor tyrosine kinase, HTK on human erythroid progenitor cells." Blood. 89. 2757-2765 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakamoto O.: "Role of macrophage-stimulating protein and its receptor, RON tyrosine kinase in ciliary motility." J Clin Invest. 99. 701-709 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirao A.: "Translocation of the Csk homologous kinase (Chk/Hyl) controls activity of CD36-anchored Lyn tyrosine in thrombin-stimulated platelets." EMBO J. 16. 2342-2351 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato A: "Leukocyte typing VI" Garland Publishing Inc., 1342 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hashiyama M: "Predominant expression of a receptor tyrosine kinase, TIE in hematopoietic progenitor cells and B cell line." Blood. 87. 93-101 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yano M: "Expression and function of murine orphan receptor tyrosine kinases, TIE and TEK in hemtopoietic stem cells." Blood. in press. (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iwama A: "STK/RON receptor tyrosine kinase mediates both apoptotic and growth signals via the multifunctional docking site conserved among HGF receptor familty." EMBO J. 15. 5866-5876 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sahamoto O: "The role of macrophage-stimulating protein its receptor, RON tyrosine kinase in ciliary motility." J Clin Invest. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Inada T: "Selective expression of the receptor tyrosine kinase, HTK on erythroid progenitors of human bone marrow." Blood. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hirao A: "Translocation of the Csk homologous kinase (Chk/Hyl) regulates CD36-anchored Src-family kinases in platelet activation" EMBO J. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakano S: "Bone Marrow Transplantation" Springer, 331 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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