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MOLECULAR BASIS OF STEM CELL SYSTEMS AND ITS APPLICATION

Research Project

Project/Area Number 14207006
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

NAKANO Toru  OSAKA UNIVERSITY, DMCB, RESEARCH INSTITUTE FOR MICROBIAL DISEASES, PROFESSOR, 微生物病研究所, 教授 (00172370)

Co-Investigator(Kenkyū-buntansha) KIMURA Tohru  OSAKA UNIVERSITY, DMCB, RESEARCH INSTITUTE FOR MICROBIAL DISEASES, ASSOCIATE PROFESSOR, 微生物病研究所, 助教授 (50280962)
岡部 勝  大阪大学, 遺伝情報実験センター, 教授 (30089875)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥44,590,000 (Direct Cost: ¥34,300,000、Indirect Cost: ¥10,290,000)
Fiscal Year 2003: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2002: ¥31,850,000 (Direct Cost: ¥24,500,000、Indirect Cost: ¥7,350,000)
Keywordscell differentiation / stem cell / hematopoiesis / transcription factor / embryonic stem cell / macrophage / erythrocyte / megakaryocyte / 生殖細胞 / 転写調節
Research Abstract

In order to reveal the molecular differentiation mechanisms in stem cell systems, we established a novel experimental strategy combining an ES cell in vitro differentiation method (OP9 system) and Tet-off conditional gene expression method. Using the system, we analyzed the functions of transcriptional factors and co-factors involved in hematopoietic differentiation such as GATA-1, GATA-2, Runx-1 and FOG-1.
During the course of hematopoietic differentiation in the presence of M-CSF (macrophage-colony stimulating factor), macrophages are preferentially produced. When a hematopoietic zinc finger protein, GATA-2, is over-expressed, macrophage differentiation is blocked and differentiation switch to erythroid or megakaryocytic lineages occurs. And the determination to. erythroid cells or megakaryocytes were determined by the timing of GATA-2 expression. In addition, TSA (trichostatin A), an HDAC (histone de-acetylase) inhibitor skewed the differentiation from megakaryocyte to erythroid lineage. Further analyses revealed that expression level of PU.1, another hematopoietic transcription factor, played crucial roles for the lineage determination to erythroid or megakaryocytic lineages.
Now the functions of the other transcription factors are under investigation.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Suzuki A, Kaisho T, (6 authors), Nakano T: "Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination"J Exp Med. 197. 657-667 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura T, Suzuki A, (7 authors), Nakano T: "Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production"Development. 130. 1691-1700 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura T, Ito C, (11 authors), Nakano T: "Mouse Germ Cell-Less as an essential component for nuclear integrity"Mol Cell Biol. 23. 1304-1315 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A, Itami A, (8 authors), Nakano T: "Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation"Cancer Res. 63. 674-681 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano T: "Hematopoietic stem cells : generation and manipulation"Trends Immunol. 24. 589-594 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuramochi-Miyagawa K, Kimura T, (10 authors), Nakano T: "mili, a mammalian member of piwi family gene, is essential for spermatogenesis"Development. 131. 839-849 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 仲野 徹: "幹細胞とクローン"羊土社. 115 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato M, Kimura T, Kurokawa K, Fujita Y, Abe K, Masuhara M, Yasunaga T, Abe R, Yamamoto N, Nakano T.: "Identification of PGC7, a new gene expressed specifically in preimplantation embryos and germ cells."Mech Dev. 113. 91-94 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima K, Masuhara M, Era T, Enver T, Nakano T.: "GATA-2 and GATA-2IER display opposing activities in the development and differentiation of blood progenitors."EMBO J. 21. 3060-3069 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura T, Ito C, Watanabe S, Takahashi T, Ikawa M, Yomogida K, Ikeuchi M, Asada N, Fujita Y, Matsumiya K, Okuyama A, Okabe M, Toshimori K, Nakano T.: "Mouse Germ Cell-Less as an essential component for nuclear integrity."Mol Cell Biol. 23. 1304-1315 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A, Itami A, Ohishi M, Inoue T, Komazawa N, Senoo H, Sasaki T, Takeda J, Manabe M, Mak TW, Nakano T.: "Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation."Cancer Res. 63. 674-681 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A, Kaisho T, Ohishi M, Tsukio-Yamaguchi M, Tsubata T, Koni PA, Sasaki T, Mak TW, Nakano T.: "Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination"J Exp Med. 197. 657-667 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kimura T, Suzuki A, Fujita Y, Yomogida K, Lomeli H, Asada N, Ikeuchi M, Nagy A, Mak TW, Nakano T.: "Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production"Development. 130. 1691-1700 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitajima K, Tanaka M, Jie Z, Sakai-Ogawa E, Nakano T.: "In vitro differentiation of mouse embryonic stem cells to hematopoietic cells on an OP9 stromal cell monolayer"Methods Enzymol. 365. 72-82 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano T: "Hematopoietic stem cells: generation and manipulation"Trends Immunol. 24. 589-594 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Masuhara M, Nagao K, Nishikawa M, Kimura T, Nakano T: "Enhanced degradation of MDM2 by a nuclear envelope component, mouse germ cell less"Biochem Biophys Res Commun. 308. 927-932 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Payer B, Saitou M, Barton SC, Thresher R, Dixon JPC, Zahn D, College WH, Canton MBL, Nakano T, Saran MA.: "Stella is a maternal effect gene required for normal early development in mice"Cur Biol. 13. 2110-2117 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ueno H, Sakita-Ishikawa M, Morikawa Y, Nakano T, Kitamura T, Saito M.: "A stromal cell-derived membrane protein that supports hematopoietic stem cells"Nature Immunol. 4. 457-463 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuki A, Kaisho T, (6 authors), Nakano T.: "Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination"J Exp Med. 197. 657-667 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura T, Suzuki A, (7 authors), Nakano T: "Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production"Development. 130. 1691-1700 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kimura T, Ito C, (11 authors), Nakano T.: "Mouse Germ Cell-Less as an essential component for nuclear integrity"Mol Cell Biol. 23. 1304-1315 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuki A, Itami A, (8 authors), Nakano T: "Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, acceleraled hair follicle morphogenesis and tumor formation"Cancer Res. 63. 674-681 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakano T: "Hematopoietic stem cells : generation and manipulation"Trends Immunol. 24. 589-594 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuramochi-Miyagawa K, Kimura T, (10 authors), Nakano T: "mili, a mammalian member of piwi family gene, is essential for spermatogenesis"Development. 131. 839-849 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 仲野 徹: "幹細胞とクローン"羊土社. 115 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanigaki T, (5), Nakano T, Honjo T.: "Notch/RBPJ signaling is involved in cell fate determination of Marginal Zone B cells"Nature Immunol. 3. 443-450 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitajima K, (2), Nakano T.: "GATA-2 and GATA-2/ER display opposing activities in the development and differentiation of blood progenitors"EMBO J. 21. 3060-3069 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitamura T, (12), Nakano T.: "Mouse Germ Cell-Less as an essential component for nuclear integrity"Mol Cell Biol. 23. 1304-1315 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki A, (7), Nakano T.: "Critical roles of Pten in B cell homeostasis and immunoglobulin class switch recombination"J Exp Med. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kimura T, (8), Nakano T.: "Conditional loss of PTEN leads to testicular teratoma and enhances embryonic germ cell production"Development. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki A, (9), Nakano T.: "Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation"Cancer Res. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 仲野 徹: "幹細胞とクローン"羊土社. 116 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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