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Molecular mechanisms for regulation of hematopoietic stem cells and leukemic stem cells

Research Project

Project/Area Number 16590964
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionKanazawa University (2005)
Keio University (2004)

Principal Investigator

HIRAO Atsushi  Kanazawa University, Division of Molecular Genetics, Cancer Research Institute, professor, がん研究所, 教授 (90343350)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordshematopoietic stem cell / leukemia / SP細胞
Research Abstract

We demonstrated that side population (SP), based on FACS analysis with Hoechst33342, in c-kit+Sca-1+Lin-(KSL) cells represents a population of quiescent hematopoietic stem cells (HSCs). Cell cycle analysis with BrdU labeling showed that SP were slowly cycling in GO phase. HSCs mobilized in peripheral blood from a bone marrow niche by G-CSF or 5-FU treatment were cycling and those cycling HSCs were not in SP.HSCs in developing mice, which were cycling and expanding, were also in main population (MP). SP cells in KSL fraction were resistant to myelosuppressive stress including X-ray and 5-FU treatment which depletes cycling hematopoietic cells. Histological examination revealed that the 5-FU resistant HSCs were surrounded by bone-lining osteoblast-like cells on the surface of the bone. These data indicate that the osteoblastic zone is a niche for quiescent HSCs in bone marrow. Recently tumorigenic or tumor-initiating cells, which are called cancer stem cells, have been identified. We attempted to identify cancer stem cells by using SP fraction. We established leukemia model by retroviral infection carrying HoxA9 and Meis1. The leukemia cells included SP cells in bone marrow. However transplantation experiments did not showed the evidence showing that leukemic stem cells were enriched in SP fraction. These data suggest requirement of another markers for identification of cancer stem cells.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells2006

    • Author(s)
      Ito K.他
    • Journal Title

      Nature Medicine 12・4

      Pages: 446-451

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells2006

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

      Nature Medicine 12(4)

      Pages: 446-451

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells2006

    • Author(s)
      Ito K, Hirao A(他9名)
    • Journal Title

      Nature Medicine (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A quantitative matrigel assay for assessing repopulating capacity of prostate stem cells.2005

    • Author(s)
      Azuma M, 他
    • Journal Title

      Biochem Biophys Res Commun. 338・2

      Pages: 1164-1170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A quantitative matrigel assay for assessing repopulating capacity of prostate stem cells.2005

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

      Biochem Biophys Res Commun. 338(2)

      Pages: 1164-1170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A quantitative matrigel assay for assessing repopulating capacity of prostate stem cells.2005

    • Author(s)
      Azuma M, Hirao A(他4名)
    • Journal Title

      Biochem Biophys Res Commun. 338・2

      Pages: 1164-1170

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulation of oxidative stress by ATM is required for the self-renewal of haematopoietic stem cells.2004

    • Author(s)
      Ito K.他
    • Journal Title

      Nature 431・7011

      Pages: 997-1002

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche.2004

    • Author(s)
      Arai F.他
    • Journal Title

      Cell 118・2

      Pages: 149-161

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Collaboration of Brca1 and Chk2 in tumorigenesis.2004

    • Author(s)
      McPherson J.P.他
    • Journal Title

      Genes Dev. 18・10

      Pages: 1144-1153

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Regulation of oxidative stress by ATM is required for the self-renewal of haematopoietic stem cells.2004

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

      Nature 431(7011)

      Pages: 997-1002

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 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, Hirao A. et al.
    • Journal Title

      Cell 118(2)

      Pages: 149-161

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Collaboration of Brcal and Chk2 in tumorigenesis.2004

    • Author(s)
      McPherson JP, Lemmers B, Hirao A, et al.
    • Journal Title

      Genes Dev 18(10)

      Pages: 1144-1153

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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