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生殖系幹細胞の自己複製制御機構の解明

Research Project

Project/Area Number 18051005
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionChiba University

Principal Investigator

岩間 厚志  Chiba University, 大学院・医学研究院, 教授 (70244126)

Co-Investigator(Kenkyū-buntansha) 宮城 聡  千葉大学, 大学院・医学研究院, 助教 (20400997)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2007: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥3,600,000 (Direct Cost: ¥3,600,000)
Keywordsポリコーム遺伝子 / 精子幹細胞 / 自己複製 / Bmil / Ring1b / Bmi1
Research Abstract

ポリコーム群蛋白質はクロマチン修飾因子としてエピジェネティックな遺伝子発現抑制を担う分子群であり、核内でPRC1とPRC2の2つの複合体を形成する。今回、我々はPRC1構成因子Bmi1とRing1Bの精子幹細胞における機能解析を行った。Bmi1ノックアウト(KO)マウスの精巣は形態的には野生型と変わりなく、精子への分化も正常に見られた。前回の班会議ではBmi1KOマウス由来の精子幹細胞移植において再構築能の異常を報告したが、今回W/W^vを用いて再評価したところ、特に異常は認められず、Bmi1KO精子幹細胞の自己複製能はほぼ正常であると考えられた。一方、生殖幹細胞におけるRing1Bの役割を検討するため、Ring1B^<FL/FL>マウスとTNAP-Creマウスを交配し得られたコンディショナルノッククアウト(Ring1B^<FL/FL>;TNAP-Cre)の精巣を経時的に解析した。この結果、生後3週からRing 1B^<FL/FL>;TNAP-Creの一部の精細管に形態異常が認められ始め、10週では約4割の精細管において生殖細胞が消失していた。Ring1B^<FL/FL>;TNAP-CreにおけるRing1Bの発現は、胎生期より減少・消失していると考えられるが、生後1週では、コントロールマウスとRing1B^<FL/FL>;TNAP-Creの精巣の形態やPLZF陽性細胞数に大きな違いが認められなかった。従って、成獣で認められる異常は、胎生期における発生異常ではなく、生後の精子幹細胞の増幅異常によるものと考えられる。しかし、25週令のマウスにおいても約6割の精細管では生殖細胞が維持されていることから、Ring1Bは幹細胞の維持に必ずしも必要ではないと考えられる。以上の結果は、Ring1B欠損精子幹細胞の異常が環境側の要因による可能性も示唆しており、今後、発現がより精子幹細胞に限局しているngn-3-Creを用いたRing1B遺伝子欠損による効果を検討する予定である。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2008 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 8 results) Presentation (3 results)

  • [Journal Article] Role for derepressed p57^<Kip2> in a loss of self-renewing hematopoietic stem cells in Bmil-deficient mice.2008

    • Author(s)
      Oguro H.
    • Journal Title

      Blood Cells Mol Dis (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bmil regulates memory CD4 T cell survival via repression of the Noxa gene.2008

    • Author(s)
      Yamashita M.
    • Journal Title

      J Exp Med (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of transcripts commonly expressed in hematopoietic and germline stem cells.2008

    • Author(s)
      Mizukami T.
    • Journal Title

      Stem Cells and Development. 17

      Pages: 67-80

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clonal expansion of non-leukemic cells expressing two novel MLL-ELL variants differing in transfonrming activity.2007

    • Author(s)
      Takeuchi M.
    • Journal Title

      Leukemia 22

      Pages: 861-864

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Excessive self-renewal of hepatic stem/progenitor cells drives cancer initiation.2007

    • Author(s)
      Chiba T.
    • Journal Title

      Gastroenterology 133

      Pages: 937-950

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Life and death in hematopoietic stem cells.2007

    • Author(s)
      Oguro H.
    • Journal Title

      Curr Opin Immunol 19

      Pages: 503-509

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo.2007

    • Author(s)
      Oyama T.
    • Journal Title

      Proc Natl Acad Sci USA, 2007 104

      Pages: 9764-9769

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine signaling, lipid raft clustering and HSC hibernation.2007

    • Author(s)
      Yamazaki S.
    • Journal Title

      Ann N Y Acad Sci. 1106

      Pages: 54-63

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cooperative interaction between Ets1 and Gfi1 transcriptional factors in repression of bax gene expression.2007

    • Author(s)
      Nakazawa Y.
    • Journal Title

      Oncogene

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Unique composition of polycomb repressive complex 1 in hematopoietic stem cells.2007

    • Author(s)
      Kato Y.
    • Journal Title

      Int. J Hematol. 85

      Pages: 179-181

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bmil cooperates with Dnmtl associated protein 1 in gene silencing.2006

    • Author(s)
      Negishi M.
    • Journal Title

      Biochem. Biophys. Res. Comm. 353

      Pages: 992-998

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Differential impact of Ink4α and Arf on hematopoietic stem cells and their bone marrow microenvironment in Bmil-deficient mice.2006

    • Author(s)
      Oguro H.
    • Journal Title

      J. Exp. Med. 203

      Pages: 2247-2253

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Putative "stemness" gene Jam-B is not required for maintenance of stem cell state in embryonic, neural, or hematopoietic stem cells.2006

    • Author(s)
      Sakaguchi T.
    • Journal Title

      Mol. Cell. Biol. 26

      Pages: 6557-6570

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytokine signals modulated via lipid rafts mimics niche signals and induce hibernation in hematopoietic stem cells.2006

    • Author(s)
      Yamazaki S.
    • Journal Title

      EMBO J. 25

      Pages: 3515-3523

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Side population purified from hepatocellular carcinoma cells harbors cancer stem cell-like properties.2006

    • Author(s)
      Chiba T.
    • Journal Title

      Hepatology 44

      Pages: 240-251

    • Related Report
      2006 Annual Research Report
  • [Journal Article] MOZ is essential for maintenance of hematopoietic stem cells.2006

    • Author(s)
      Katsumoto T.
    • Journal Title

      Genes & Dev. 20

      Pages: 1321-1330

    • Related Report
      2006 Annual Research Report
  • [Presentation] The polycomb gene product Bmil is essential for the tumor-initiating capacity of hepatocellular carcinoma cells.2008

    • Author(s)
      岩間厚志
    • Organizer
      第5回国際幹細胞学会
    • Place of Presentation
      Cairns Convention Centre
    • Year and Date
      2008-06-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] ポリコーム遺伝子Bmilによる癌幹細胞の自己複製制御2008

    • Author(s)
      岩間厚志
    • Organizer
      第6回日本臨床腫瘍学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Year and Date
      2008-03-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] 前駆細胞が癌幹細胞化する過程における自己複製制御分子Bmilの機能2008

    • Author(s)
      岩間厚志
    • Organizer
      第7回日本再生医療学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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