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Determination and differentiation of heamtopoietic stem cell toward T, B and myeloid cell lineages

Research Project

Project/Area Number 09557029
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KATSURA Yoshimoto  Institute for Frontier Medical Science Professor, 再生医科研究所, 教授 (90027095)

Co-Investigator(Kenkyū-buntansha) TAMURA Masahiko  Chugai Pharmaceutical Co., LTD. Researcher, 創薬研究所, 主任研究員
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1997: ¥5,600,000 (Direct Cost: ¥5,600,000)
Keywordshematopoietic stem cell / differentiation / commitment / T cell / thymus / AGM region / lineage committed progenitor / 決定 / B細胞 / ミエロイド細胞
Research Abstract

By using the multilineage progenitor (MLP) assay, which is able to determine the developmental capability of hematopoietic progenitors toward myeloid (M), T and B cell lineages, we have identified various types of progenitors in murine fetal liver (FL). The progenitor types detected were multipotent progenitors (p-MTB), bipotent progenitors generating M and T cells (p-MT) or M and B cells (p-MB), and unipotent progenitors generating M(p-M), T(p-T) or B(p-B) cells. Since p-TB type was defective, p-T and p-B were thought to be derived from p-MTB via p-MT and p-MB, respectively. These findings provided an opportunity to reconsider the process of hematopoiesis; it is improbable that the lineage commitment progresses stochastically, but it should progress deterministically. It was further shown that p-T emerge ontogenically earlier than p-B in FL, and moreover that all six types of progenitors are already produced in the aorta-gonad-mesonephros (AGM) region of day 10 fetuses. Although the p-MTB in AGM region do not have long-term reconstitution (LTR) activity, these p-MTB was found to acquire the LTR activity by culturing with a stromal cell line. Thymic earliest p-T are still multipotent in that they are able to generate dendritic cell (DC) and NK cells. These DC and NK potentials are release with the progress of intrathymic developmental stages.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Kawamoto,H. et al.: "Emergence of T cell lineage restricted progenitors at the earliest stage of hematopoiesis in the murine fetal liver"Journal of Immunology. 162 5. 2725-2731 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Van Ewijk,W., et al.: "Thymic miroenvironments, 3-D versus 2-D?"Seminars in Immunology. 11 1. 57-64 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawabata,K. et al.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc.Natl. Acad. Sci. USA. 96 10. 5663-5667 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohmura,K. et al.: "Emergence of T,B and myeloid lineage commitment as well as multipotent hematopoietic progenitors in the AGM region of day 10 fetuses of the mouse"Jounral of Immunology. 163 9. 4788-4795 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikawa,T.et al.: "Commitment of common T/NK progenitors to unipotent T and NK progenitor in the murine fetal thymus revealed by a single progentitor assay"Journal of Experimental Medicine. 190 11. 1617-1625 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawamoto,H. et al.: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawamoto, H. et al: "Emergence of T cell lineage lineage restricted progenitors at the earliest stage of hemaopiesis in the murine fetal liver"Journal of Immunology. 162(5). 2725-2731 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] van Ewijk, W., et al: "Thymic miroenvironments, 3-D versus 2-D ?"Seminars in Immunology. 11(1). 57-64 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawabata, K. et al: "A cell-autonomous requirement for CXCR4 in long-term USA lymphoid and myeloid reconstitution"Proc, Natl. Acad. Sci. 96(10). 5663-5667 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohmura, K. et al: "Emergence of T, B and myeloid lineage commitment as well as multipotent hematopoietic progenitors in the AGM region of day 10 fetuses of the mouse"Jounral of Immunology. 163(9). 4788-4795 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ikawa, T.et al: "Commitment of common T/NK progemotprs tp unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay"Journal of Experimental Medicine. 190(11). 1617-1625 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawamoto, H. et al: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawamoto H.et al.: "Emergence of T cell lineage restricted progenitors at the earliest stage of hematopoiesis in the murine etal liver"Journal of Immunology. 162・5. 2725-2731 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] van Ewijk W.et al.: "Thymic miroenvironments, 3-D versus 2-D ?"Seminars in Immunology. 11・1. 57-64 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawabata K.et al.: "A cell-autonomous requirement for CXCR4 in long-term lymphoid and myeloid reconstitution"Proc. Natl. Acod. Sci. USA. 96・10. 5663-5667 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohmura K.et al.: "Emergence of T, B and myeloid lineage commitment as well as multipotent hematopoietic progenitors in the AGM region of day 10 fetuses of the mouse"Jounral of Immunology. 163・9. 4788-4795 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikawa T.et al.: "Commitment of common T/NK progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay"Journal of Experimental Medicine. 190・11. 1617-1625 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamoto H.et al.: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nishikawa,S-I.et al.: "In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos." Immunity. 8. 761-769 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamoto,H.et al.: "Presence of progenitors restricted to T,B or myeloid lineage but absence of multipotent stem cells in the murine fetal thymus." Journal of Immunology. 161・8. 3799-3802 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takayama,E.et al.: "Enhancement of activation-induced cell death by fibronectin in murine CD4^+CD8^+ thymocytes." Immunology. 95. 553-558 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamoto,H.,et al.: "Emergence of T cell lineage restricted progenitors at the earliest stage of hematopoiesis in the murine fetal liver." Journal of Immunology. 162・5. 2725-2731 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] van Ewijk,W.,et al.: "Thymic miroenvironments,3-D versus 2-D?" Seminars in Immunology. 11. 57-64 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 桂 義元: "胸腺とT細胞" 医学書院, 197 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamoto,H.et al.: "Hematopoietic progentiorsin the murine fetal liver capable of rapidly enerating T cells" Journal of Immunology. 158・7. 3118-3124 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawamoto,H.et al.: "Direct evidence for the commitment of hematopoietic stem cells to T,B and myeloid Iineages in murine fetal liver" International Immunology. 9・7. 1011-1019 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Satoh,A.et al.: "Characterization of human p33/41 (Annexin IV),a Ca_+ dependent carobohydrate-binding protein with monoclonal anti-annexin IV antibodies,ASII and AS17" Biol Pharm Bull. 20・3. 224-229 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sawamura,T.et al.: "An endothelial receptor for oxidized low-density lipoprotein" Nature. 386・1. 73-77 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Watanabe,Y.et al.: "T cell progenitors in the murine fetal liver : Differences from those in the adult bone marrow" Cell.Immunol.177・1. 18-25 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okamoto,Y.et al.: "In SCID-hmice passivetransfer of a humanizedantibody prevents infectionand atophic change of medulla in humanthymicimplanduu to intnvenous inoculation of primary HIV-1 isdate" Journal of Immunology. 160・1. 69-76 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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