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1998 Fiscal Year Final Research Report Summary

Cloning of Molecules Supporting Self-renewal of Hematopoietic Stem Cells

Research Project

Project/Area Number 09357007
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Pediatrics
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAHATA Tatutoshi  The University of Tokyo, The Insutitute of Medical Science, Professor, 医科学研究所, 教授 (20110744)

Co-Investigator(Kenkyū-buntansha) WATANABE Sumiko  The University of Tokyo, The Insutitute of Medical Science, Research Associate, 助手 (60240735)
MAEKAWA Taira  The University of Tokyo, The Insutitute of Medical Science, Lecturer, 医科学研究所, 講師 (80229286)
TSUJI Kohichiro  The University of Tokyo, The Insutitute of Medical Science, Assocate Professor, 医科学研究所, 助教授 (50179991)
Project Period (FY) 1997 – 1998
KeywordsSelf-renewal Factor / Mouse / Hematopoietic Stem Cell / Homan / AGM Region / Stromal Cell Line / CD34+ Cell / Cloning
Research Abstract

Recent studies on the developing mouse embryo have shown that long term-repopulating hematopoietic stem cells (LTR-HSC) are first identified in aorta-gonad-mesonephros (AGM) region at 10 days postcoitum (dpc), prior to such activity being observed in yolk sac and fetal liver, and expand in 11 dpc AGM region, suggesting that the AGM region at 10 to 11 dpc expresses the molecule(s) capable of supporting the expansion of HSC.In the present study, to detect such molecules, we established three stromal cell lines from 10.5 dpc AGM region, AGM-S1, S2 and S3 cells. The AGM-S3 cells possessed the capability to support the expansion of hematopoietic progenitors in culture with murine bone marrow cells without additional cytokines. The coculture of sorted mouse hematopoietic progenitors with AGM-S3 cells showed that these expanded progenitors were derived from lineage markars-negative (Lin^-) c-Kit^+Sca-1^+ primitive hematopoietic cells. AGM-S3 cells also supported for 6 weeks generation of huma … More n multipotential progenitors from CD34^+CD38^- primitive hematopoietic cells. Human LTR-HSC with the potential to reconstitute hematopoiesis in NOD/SCID mice were maintained on AGM-S3 cells for at least 4 weeks. Flowcytometric analysis showed that CD13, vascular cellular adhesion molecule-1 and Sca-1 were expressed on AGM-S3 cells. Although AGM-S3 cell expressed stem cell factor, Interleukin (IL)-6 and oncostatin M in reverse transcription polymerase chain reaction analysis, the combination of these cytokines could not stimulate the growth of human primitive hematopoietic cells. Therefore, AGM-S3 cells seem to express species-cross reactive molecule(s) other than the cytokines examined, which act on primitive hematopoietic progenitor/stem cells. This cell line is expected to elucidate molecular mechanisms regulating early hematopoiesis, and pave the way for developing strategies for expansion of human transplantable HSC.The cloning of the molecules expressing self-renewal factors on AGM-S3 cells are now under going. Less

  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Manabe A.,Mori T.,Ebihara Y.,Nakahata T.,et al: "Characterization of leukemic cells in CD2/CD19 double positive acute lymphoblastic leukemia." Int.J.Hematol.67. 45-52 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mukouyama Y.,Hara T.,Xu M.,Nakahata T.,et al: "Induction of hematopoiesis by oncostatin M in the AGM region." Immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toru H.,Eguchi M.,Yata J.,Nakahata T.,et al: "IL-4 promotes the development of tryptase and chymase double positive human mast cells accompanied with cell maturation." Blood. 91. 187-19〓 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahata T.: "Characteristics of hemopoietic stem/progenitor cells in bone marrow,peripheral blood and cord blood." Int.J.Pediatr.Hematol.Oncology. 5. 60-61 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T.,Yamada K.,Nakahata T.,Hirai H.,et al: "A novel molecular approach to ex vivo hematopoietic expansion with recombinant EGFR-expressing adenovirus vector." Blood. 91. 4509-4515 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishihara M.,Wada Y.,Nakahata T.,Maekawa T.,et al: "A combination of stem cell factor and granulocyte colony-stimulating factor enhances the growth of human progenitor B cells supported by murine stromal cell line MS-5." Eur.J.Immunol.28. 855-864 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsuji K.,Muraoka K.,Nakahata T.,et al: "Interferon-g and human megakaryopoiesis." Leukemia and Lymphoma. 31. 107-113 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tajika K.,Ikebuchi K.,Nakahata T.,Asano S.,et al: "IL-6 and SCF exart different effects on megakaryocyte maturation." Brit. J.Haematol.100. 105-111 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishiguro A.,Ishikita T.,Naritake S.,Nakahata T.,et al: "Elevation of serum thrombopoietin precedes thrombocytopoiesis in Kawasaki disease." Thromb.Haemostasis. 79. 1096-1100 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshida K.,Taga T.,Nakahata T.,Kishimoto T.,et al: "Myocardial,hematological,and placental disorders caused by targeted disruption of gpl30,acommon signal transducer for IL-6 family of cytokines." Contemporary Immunology. 259-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki H.,Takei M.,Nakahata T.,Fukamachi H.,et al: "Inhibitory effect of adenosine on degranulation of human cultured mast cells upon cross-linking of FceRI." Biochem.Biophy.Res.Comm.242. 697-702 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato T.,Watanabe S.,Tsuji K.,Nakahata T.,et al: "Induction of the erythropoietin receptor gene and acquisition of responsiveness to erythropoietin by stem cell factor in HML/SE,a human leukemic cell line." J.Biol.Chem.273. 16921-16926 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maruyama K.,Tsuji K.,Kodera Y.,Nakahata T.,et al: "Characterization of peripheral blood progenitor cells mobilized by Nartograstim (N-terminal replaced granulocyte colony-stimulating factor) in normal volunteers." Bone Marrow Transplant.22. 313-320 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Xu M.,Tsuji K.,Miyajima A.,Nakahata T.,et al: "Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cells." Blood. 192. 2032-2040 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shichijo M.,Nakahata T.,Saito H.,Nagai H.,et al: "The effect of anti-asthma drags on mediator release from cultured human mast cells." Clin.Exp.Allergy. 28. 1229-123〓 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sako M.,Nakahaat T.,Kishitomo T.,Sugiyama H.,et al: "Abnormal expression of Wilms'tumor gene WT1 in juvenile chronic myeloid leukemia and iufantile monosomy 7 syndrome." Leukemia Res.22. 965-967 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toru H.,Pawankar R.,Yata J.,Nakahata T.,et al: "Human mast cells produce interleukin-13 by high affinity IgE receptor cross-linking : enhanced IL-13 production by IL-4 primed human mast cells." J.Allergy and Clin.Immunol.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang FC,Watanabe S.,Ebihara Y.,Nakahata T.,et al: "Human G-CSF stimulates the development of primitive multipotential progenitors of human G-CSF receptor-transgenic mice,but does not affect their commitment in vitro and in vivo." Blood. 92. 1632-1640 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahata T.,Sui X., Kishimoto T.,et al: "Ex vivo expansion of human primitive hemopoietic progenitors." Stem Cells.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sui X.,Tsuji K.,Kishimoto T.,Nakahata T.,et al: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis from human CD34+ cells through gpl30 signaling." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang FC.,Tsuji K.,Ikeda Y.,Nakahata T.,el al: "Effects of human granulocyte colony-stimulating factor (hG-CSF) on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Taniguchi T.,Endo H.,Nakahata T.,Motokura T.,et al: "Expression of p21Cip1/Waf1/Sdi1 and p27 Kip1 cyclin-dependent kinase inhibitors during human hematopoiesis." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Duraisamy K.,Saito H.,Tsujj K.,Nakahata T.,et al: "Characterization of mast-cell-committed progenitors present in human cord blood." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakahata T.,Toru H.,et al: "Development of human mast cells." Adv.Immunol.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hasegawa S.,Nakahata T.,Okumura K.,Ra C.,et al: "Functional expression of the high affinity receptor for IgE (FC epsilon RI) in human platelets and its intracellular expression in human megakaryocytes." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hibino H.,Tani K.,Nakahata T.,Asano S.,et al: "Common Mamoset as a target preclinical primate for cytokine and gene therapy studies." Blood. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kobayashi M.,Ueda K.,Nishihira H.,Nakahata T.,et al: "Serum granulocyte colony-stimulating factor levels in patients with chronic neutropenia of childhood : Modulation of G-CSF levels by myeloid precursor cell mass." Brit.J.Haematol.(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Manabe A., Mori T., Ebihara Y., Nakahata T., et al.: "Characterization of leukemic cells in CD/CD19 double positive acute lymphoblastic leukemia." Int.J.Hematol.67. 45-52 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mukouyama Y., Hara T., Xu M., Nakahata., et al.: "Induction of hematopoiesis by oncostatin M in the AGM region." Immunity. 8. 105-114 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toru H., Eguchi M., Yata J., Nakahata T., et al.: "IL-4 promotes the development of tryptase and chymase double positive human mast cell accompanied with cell maturation." Blood. 91. 187-195 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahata T.: "Characteristics of hemopoietic stem/progenitor cells in bone marrow, peripheral blood and cord blood." Int.J.Pediatr.Hematol.Oncology. 5. 60-61 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T., Yamada K., Nakahata T., Hirai H., et al.: "A novel molecular approach to ex vivo hematopoietic expansion with recombinant EGFR-expressing adenovirus vector." Blood. 91. 4509-4515 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishihara M., Wada Y., Nakahata T., Maekawa T., et al.: "A combination of stem cell factor and granulocyte colony-stimulating factor enhances the growth of human progenitor B cells supported by murine stromal cell line MS-5." Eur.J.Immunol.28. 855-864 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsuji K., Muraoka K., Nakahata T., et al.: "Interferon-g and human megakaryopoiesis." Leukemia and Lymphoma. 31. 107-113 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tajika K., Ikebuchi K., Nakahata T., Asano S., et al.: "IL-6 and SCF exart different effects on megakaryocyte maturation." Brit.J.Haematol.100. 105-111 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishiguro A., Ishikita T., Naritake S., Nakahata T., et al.: "Elevation of serum thrombopoietin precedes thrombocytopoiesis in Kawasaki disease." Thromb.Haemostasis. 79. 1096-1100 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshida K., Taga T., Nakahata T., Kishimoto T., et al.: "Myocardial, hematological, and placental disorders caused by targeted disruption of gp130, acommon signal transducer for IL-6 family of cytokines." Contemporary Immunology.259-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki H., Takei M., Nakahata T., Fukamachi H., et al.: "Inhibitory effect of adenosine on degranulation of human cultured mast cells upon cross-linking of FceRI." Biochem.Biophy.Res.Comm.697-702 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato T., Watanabe S., Tsuji K., Nakahata T., et al.: "Induction of the erythropoietin receptor gene and acquisition of responsiveness to erythropoietin by stem cell factor in HML/SE,a human leukemic cell line." J.Biol.Chem.273. 16921-16926 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maruyama K., Tsuji K., Kodera Y., Nakahata T., et al.: "Characterization of peripheral blood progenitor cells mobilized by Nartograstim (N-terminal replaced granulocyte colony-stimulating factor) in normal volunteers." Bone Marrow Transplant.22. 313-320 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Xu.M., Tsuji K., Miyajima A., Nakahata T., et al.: "Stimulation of mouse and human primitive hematopoiesis by murine embryonic aorta-gonad-mesonephros-derived stromal cells." Blood. 192. 2032-2040 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shichijo M., Nakahata T., Saito H., Nagai H., et al.: "The effect of anti-asthma drags on mediator release from cultured human mast cells." Clin.Exp.Allergy. 28. 1229-1236 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sako M., Nakahata T., Kishitomo T., Sugiyama H., et al.: "Abnormal expression of Wilms'tumor gene WT1 in juvenile chronic myeloid leukemia and infantile monosomy 7 syndorome." Leukemia Res.22. 965-967 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toru H., Pawankar R., Yata J., Nakahata T., et al.: "Human mast cells produce interleukin-13 by high affinity IgE receptor cross-linking : enhanced IL-13 production by IL-4 primed human mast cells." J.Allergy and Clin.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang FC,Watanabe S., Ebihara Y., Nakahata T., et al.: "Human G-CSF stimulates the development of primitive multipotential progenitors of human G-CSF receptor-transgenic mice, but does not affect their commitment in vitro and in vivo." Blood. 92. 1632-1640 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahata T., Sui X., Kishimoto T., et al.: "Ex vivo expansion of human primitive hemopoietic progenitors." Stem Cells.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sui X., Tsuji K., Kishismoto T., Nakahata T., et al.: "Soluble IL-6 receptor with IL-6 stimulates megakaryopoiesis from human CD34+ cells through gp130 signaling." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang FC., Tsuji K., Ikeda Y., Nakahata T., et al.: "Effects of human granulocyte colony-stimulating factor (hG-CSF) on megakaryopoiesis and platelet function in hG-CSF receptor-transgenic mice." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Taniguchi T., Endo H., Nakahata T., Motokura T., et al.: "Expression of p21 Cip1/Waf1/Sdi1 and p27 Kip1 cyclin-dependent kinase inhibitors during human hematopoiesis." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Duraisamy K., Saito H., Tsuji K., Nakahata T., et al.: "Characterization of mast-cell-committed progenitors present in human cord blood." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahata T., Toru H., et al.: "Development of human mast cells." Adv.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hasegawa S., Nakahata T., Okumura K., Ra C., et al.: "Functional expression of the high affinity receptor for IgE (Fc epsilon RI) in human platelets and its intracellular expression in human megakaryocytes." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hibino H., Tani K., Nakahata T., Asano S., et al.: "Common Mamoset as a target preclinical primate for cytokine and gene therapy studies." Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kobayashi M., Ueda K., Nishihira H., Nakahata T., et al.: "Serum granulocyte colony-stimulating factor levels in patients with chronic neutropenia of childhood : Modulation of G-CSF levels by myeloid precursor cell mass." Brit.J.Haematol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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