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Molecular mechanisms making the difference between leukemic stem cells and hematopoietic stem cells

Research Project

Project/Area Number 16590921
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionTohoku University

Principal Investigator

MINEGISHI Naoko  Tohoku University, Biomedical Engineering Research Organization, Associate Professor, 先進医工学研究機構, 助教授 (40271895)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordshematopoietic stem cells / transcription factor / proteasome / ubiquitin / cell cycle / leukemia / 細胞死 / 蛋白質分解
Research Abstract

Leukemic stem cells, a small fraction of leukemic cells with the capacity to cause leukemia in transplanted animals, have the characteristics very similar to those of hematopoietic stem cells. The hematopoietic stem cells are the good candidates for the cell therapy and the regenerative medicine. Therefore, it is an urgent issue to elucidate the differences between the two types of stem cells, in order to handle normal stem cells ex vivo without the fear of the therapy-induced malignancies, and to find the new targets of leukemia therapies.
We have studied on the transcription factor GATA2, an indispensable factor for the proliferation and survival of the hematopoietic stem cells. Under the support of the scientific research fund, we first found the short half-life of the GATA2 protein and the contribition of the protein degradation pathway on the rapid control of GATA2 expression (1). Secondly, We carried out the transgenic mice reporter analysis, and revealed the regulatory domain driving the GATA2 gene transcription in the hematopoietic cells of murine embryos (2). This regulatory domain was only active in vivo, and had the indispensable GATA-factor binding sequences, suggesting the positive feedback regulation of GATA2 expression. Thirdly, we analyzed the green fluorescent protein (GFP) expression in the hematopoietic stem cell fraction of the mice having the genetic insertion of GFP cDNA into the transcriptional start site of GATA2 gene, and demonstrated the expression of the GFP/GATA2 and Sca1 in the long-term reconstituting hematopoietic stem cells (3,). The video imaging of the living bone marrows of these mice revealed the active "niche" structures, the previously conceptual microenvironments nursing hematopoietic stem cells. Hematopoietic stem cells attached to the osteoblasts, and seemed to receive the signals from the osteoblasts.

Report

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

    (16 results)

All 2006 2005 2004

All Journal Article (16 results)

  • [Journal Article] Combinatorial Gata2 and Scal expression defines hematopoietic stem cells in the bone marrow niche2006

    • Author(s)
      Suzuki N
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America 103・7

      Pages: 2202-2207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Important role of endogenous erythropoietin system in recruitment of endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice2006

    • Author(s)
      Satoh K
    • Journal Title

      Circulation 113

      Pages: 1442-1450

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche2006

    • Author(s)
      Suzuki N.
    • Journal Title

      Proceedings of the National Academy of Sciences of the United State of America 103・3

      Pages: 2202-2207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Combinatorial Gata2 and Sca1 expression defines hematopoietic stem cells in the bone marrow niche2006

    • Author(s)
      Suzuki N
    • Journal Title

      Proceedings of the National Academy of Sciences of the United State of America 103・7

      Pages: 2202-2207

    • Related Report
      2005 Annual Research Report
  • [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of Stat3 activity2005

    • Author(s)
      Ezoe S
    • Journal Title

      The Journal of Biological Chemistry 280・3

      Pages: 13163-13170

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Rapid turnover GATA-2 via ubiquitin-proteasome protein degradation pathway2005

    • Author(s)
      Minegishi N
    • Journal Title

      Genes to Cells 10・7

      Pages: 693-704

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] GATA motifs regulate early hematopoietic lineage-specific expression of the Gata2 gene2005

    • Author(s)
      Kobayashi-, Osaki M
    • Journal Title

      Molecular and Cellular Biology 25・16

      Pages: 7005-7020

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential effects of GATA-1 on proliferation and differentiation of erythroid lineage cells2005

    • Author(s)
      Zheng J
    • Journal Title

      Blood 107・2

      Pages: 520-527

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of Stat3 activity2005

    • Author(s)
      Ezoe S.
    • Journal Title

      The Journal of Biological Chemistry 280・3

      Pages: 13163-13170

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rapid turnover GATA-2 via ubiquitin-proteasome protein degradation pathway2005

    • Author(s)
      Minegishi N.
    • Journal Title

      Genes to Cells 10・7

      Pages: 693-704

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GATA motifs regulate early hematopoietic lineage-specific expression of the Gata2 gene2005

    • Author(s)
      Kobayashi-Osaki M.
    • Journal Title

      Molecular and Cellular Biology 25・16

      Pages: 7005-7020

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential effects of GATA-1 on proliferation-and differentiation of erythroid lineage cells2005

    • Author(s)
      Zheng J.
    • Journal Title

      Blood 107・2

      Pages: 520-527

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] GATA motifs regulate early hematopoietic lineage-specific expression of the Gata2 gene2005

    • Author(s)
      Kobayashi-Osaki M
    • Journal Title

      Molecular and Cellular Biology 25・16

      Pages: 7005-7020

    • Related Report
      2005 Annual Research Report
  • [Journal Article] GATA transcription factors inhibit cytokine-dependent growth and survival of a hematopoietic cell line through the inhibition of STAT3 activity2005

    • Author(s)
      Sachiko Ezoe
    • Journal Title

      Journal of Biological Chemisry (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ubiquitin -Proteasome -Dependent Degradation of GATA-2 and its contribution to UV-C induced Down -Regulation.2004

    • Author(s)
      Naoko Minegishi
    • Journal Title

      Blood 104

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreased expression of stem cell specific gene in Aplastic Anemia ; Possible pregulation of HOX B4 gene by GATA-2.2004

    • Author(s)
      Hisayuki Yokoyama
    • Journal Title

      Blood 104

    • Related Report
      2004 Annual Research Report

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

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