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血液幹細胞に特異的に発現される分子の発現調節とその機能解析

Research Project

Project/Area Number 03454526
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

SUDA Toshio  Jichi Med School Dept Medicine Associate Prof, 医学部, 助教授 (60118453)

Co-Investigator(Kenkyū-buntansha) 今川 重彦  自治医科大学, 医学部, 助手 (60231164)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,300,000 (Direct Cost: ¥4,300,000)
KeywordsStem cells / c-kit / CD34 / FACS / SCF / SCF / Cーkit
Research Abstract

1. The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor for stem cell factor (SCF). A monoclonal antibody against the murine c-kit molecule was prepared. Eight and 25 weeks after transplantation of Lin^-c-kit^+ cells, donor-derived cells were found in the bone marrow, spleen, thymus and peripheral blood. These data show that the c-kit molecule is expressed in multipotent stem cells and plays an essential role in the early stage of hematopoiesis.
Based on these findings, we were able to purify the murine stem cells (CFU-S).
2. To characterize and clarify the function of CD34 antigen, we isolated two types of CD34 mRNA which were generated by alternative splicing. The cDNA sequence predicted a 382 amino acid protein containing an N-terminal signal peptide and one transmembrane region 73 aminoacids from the c-terminus. Northern blot analysis using a murine cDNA probe showed that CD34 was highly expressed in the brain and testis, and moderately in the thymus, spleen and bone marrow, but not in adult liver. However, day 12 to 14 fetal liver cells showed significant expression of CD34.
3. We have cloned genomic CD34 and have a plan to examine the promoter and enhancer region. To clarify the function of CD34 molecule, we are now preparing the transgenic mice of CD34. Moreover, we are constructing the Lac Z-CD34 gene to Knock out genomic CD34. and

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] Okada,S. et al: "Sequential analysis of hemopoietic reconstitution achieved by transplantation of hemopoietic stem cells." Blood. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Miura,N. et al: "Stem cell factor and IL-6 preferentially support the proliferation of kit-positive hemopoietic progenitors rather than their differentiation." Exp.Hematol.21. 143-149 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada,S. et al: "In vivo and in vitro stem cell function of c-kit and Sca-1-positive hemopoietic cells." Blood. 80. 3044-3050 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kodama,H. et al: "In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells:Evidence for the presence of a mechanism(s)other than invoving c-kit receptor and its ligand." J.Exp.Med.176. 351-361 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Gunji,Y. et al: "Expression and function of adhesion molecules on human hemopoietic stem cells:CD34^+LFA-1^- are more primitive than CD34^+LFA-1^+ cells." Blood. 79. 429-436 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Suda,J. et al: "Two types of murine CD34 mRNA generated by alternative splicing." Blood. 79. 2288-2295 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 須田 年生: "血液幹細胞の運命" 羊土社, 141 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada S et al.: "Enrichment and characterization of murine hemopoietic stem cells which express c-kit molecule." Blood. 78. 1706-1712 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ohara A et al.: "Generation of B lymphocytes from a single hemopoietic progenitor cell in vitro." Int. Immunol.3. 703-709 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamaguchi Y et al.: "Analysis of the survival of mature human eosinophils: Increased gene expression of mitochondorial proteins by IL-5 in mature human eosinophils." Blood. 78. 2542-2547 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsunoda J-I et al: "In vivo stem cell function of interleukin-3-induced blast cells." Blood. 78. 318-322 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Gunji Y et al: "Support of early B cell differentiation in mouse fetal liver by stromal cells and interleukin-7." Blood. 77. 2612-2617 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tanaka T et al.: "Stimulatory effects of granulocyte colony stimulating factor on CFU-S differentiation and pre-CFU-S proliferation in mice." Blood. 77. 2597-2602 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kodama H et al.: "Response of newly established mouse myeloid leukemic cell lines to MC3T3-G2/PA-6 preadipocytes and hemopoietic factors." Blood. 77. 49-54 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada S et al.: "Effect of interleukin 3, interleukin 6, and granulocyte colony stimulating factor on sorted murine splenic progenitor cells." Exp. Hematol.19. 42-46 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Suda T: "Hematopoietic factors and hematological diseases." Jpn J Int Med. 30. 600-602 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamaguchi Yet al: "Effect of synthesized constituents in ltryptophan product on the differentiation of eosinophils and induction of IL-6: A possible cause of eosinophilia-myalgia syndrome." Biochem Biophysic Res Commun. 178. 1008-1013 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ema H et al.: "Multipotent and committed CD34^+ cells in bone marrow transplantation." Jpn J Cancer Res. 82. 547-552 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Komatsu N et al: "Establishment and characterization of a human leukemic cell line with megakaryocyic features: Dependency on granulocyte-macrophage colony stimulating factor, interleukin 3 or erythropoietin for growth and survival." Cancer Res.51. 341-348 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kodama H et al.: "Congenital osteoclast deficiency in osteopetrotic (op/op) mice is cured by injections of macrophage-colony stimulating factor." J Exp Med. 173. 269-272 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Honma Y et al.: "Introduction by some protein kinase inhibitors of differentiation of a mouse megakaryoblstic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus." Cancer Res. 51. 4649-4655 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Ozawa T et al.: "Reduction of RNA and hemoglobin synthesis in human erythroblasts in culture by ultrastructural cytochemical technique." J Clin Electron Microscopy. 24. 169-177 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsuda Eet al.: "Factor with erythroid burst-promoting activity in human urine unlike other hematopoietic growth factors." Int J Hematol. 54. 363-369 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada S et al: "In vivo and in vitro stem cell function of c-kit and Sca-1-positive hemopoietic cells." Blood. 80. 3044-3050 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Gunji Y et al: "Expression and function of adhesion molecules on human hemopoietic stem cells: CD34^+LFA-1^- are more primitive than CD34^+LFA-1^+ cells." Blood. 80. 429-436 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Honma Y et al.: "Herbimycin A, an inhibitor of tyrosine kinase, prolongs survival of mice inoculated with myeloid leukemia C1 cells with high expression of v-abl tyrosinekinase." Cancer Res. 52. 4017-4020 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Muroi K et al.: "Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le^x and other lactoseries type 2 chain antigens: Absence of reactivity with normal hematopoietic progenitor cells" Blood. 79. 713-719 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kodama H et al.: "In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells: Evidence for the presence of a mechanism(s) other than that involving c-kit receptor and its ligand." J. Exp. Med.176. 351-361 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Suda J et al.: "Two types of murine CD34 m RNA generated by alternative splicing." Blood. 79. 2288-2295 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada S et al.: "Synergism of IL-3 and IL-6 on highly enriched murine hematopoietic progenitors." Exp. Hematol. 20. 546-551 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shiozaki H et al.: "Suppressive effect of LD78 on the proliferation of human hemopoietic progenitors." Jpn J Cancer Res. 83. 499-504 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Muroi K et al.: "Expression of CD11b, CD14 and CD36 antigens by B-cell lymphoma." Brit J Hematol. 80. 126-127 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsuchiya T et al.: "In vitro reconstitution of an erythropoietin gene transcription system using its 5'-flanking sequence and a nuclear extract from anemic kidney." Biochem Biophysic Res Commun. 182. 137-143 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Hermine O et al.: "Granulocyte-macrophage colony stimulating and erythropoietin act competitively to induce two different programs of differentiation in the human pluripotent cell line UT-7." Bllod. 80. 3060-3069 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada Set al.: "Sequential analysis of hemopoietic reconstitution achieved by transplantation of hemopoietic stem cells." Blood.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Miura N et al.: "Stem cell factor and IL-6 preferentially support the proliferation of kit-positive hemopoietic progenitors rather than their differentiation." Exp. Hematol.21. 143-149 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamaguchi Y et al.: "Expression of c-kit mRNA and protein during the differentiation of human hematopoietic progenitor cells." Exp Hematol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Okada,S.et al: "Sequential analysis of hemopoietic reconstitution achieved by transplantation of hemopoietic stem cells." Blood. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Miura,N.et al: "Stem cell factor and IL-6 preferentially support the proliferation of kit-positive hemopoietic progenitors rather than their differentiation." Exp.Hematol.21. 143-149 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okada,S.et al: "In vivo and in vitro stem cell function of c-kit and Sca-1-positive hemopoietic cells." Blood. 80. 3044-3050 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kodama,H.et al: "In vitro proliferation of primitive hemopoietic stem cells supported by stromal cells:Evidence for the presence of a mechanism(s)other than invoving c-kit receptor and its ligand." J.Exp.Med.176. 351-361 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Gunji,Y.et al: "Expression and function of adhesion molecules on human hemopoietic stem cells:CD34^+LFA-1^- are more primitive than CD34^+LFA-1^+ cells." Blood. 79. 429-436 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suda,J.et al: "Two types of murine CD34 mRNA generated by alternative splicing" Blood. 79. 2288-2295 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 須田 年生: "血液幹細胞の運命" 羊工社, 141 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Okada,S.: "Effect of interleukin 3,interleukin 6,and granulocyte colony stimulating factor on sorted murine splenic progenitor cells." Exp.Hematol.19. 42-46 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ema,H.: "Multipotent and committed CD34^+ cells in bone marrow transplantation" Jpn.Cancer Res.82. 547-552 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tanaka,T.: "Stimulatory effects of granulocyte colony stimulating factor on CFUーS differentiation and preーCFUーS proliferation in mice." BLOOD. 77. 2597-2602 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Gunji,Y.: "Support of early B cell differentiation in mouse fetal liver by stroma cells and interleukinー7" BLOOD. 77. 2612-2617 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Tsunoda,JーI.: "In vitro stem cell function of interleukinー3ーinduced blast cells." BLOOD. 78. 318-322 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Okada,S.: "Enrichment and characterization of murine hemopoietic stem cells that express cーkit molecule." BLOOD. 78. 1706-1712 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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