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The cell diversity and the cell lineage in Shh-type medulloblastoma.

Research Project

Project/Area Number 24501325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

SUGITANI Yoshinobu  公益財団法人がん研究会, その他部局等, 研究員 (80360569)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords脳腫瘍 / 小脳髄芽腫 / miRNA / 癌幹細胞 / shh シグナル / Patched-1 / ニューロン分化 / 神経前駆細胞 / 神経分化 / shhシグナル / 髄芽腫 / 遺伝子発現制御 / Nmyc / ニューロン / 小脳腫瘍 / in vivo エレクトロポレーション / ノックアウトマウス
Outline of Final Research Achievements

Our immunohistochemical analyses and genetic lineage study showed that the medulloblastoma (MB) were composed of the MB cells of varied differentiation status, and that the cancer stem cells took the bipolar cell morphology and often differentiated into neurons with multiple dendrites like normal immature cerebellar granule neurons. We found that in MB, the expression patterns of miRNA-Xs that we have identified as the gatekeeper in MB development, were well correlated with the differentiation state of MB cells. Mis-expression of miRNA-X induced the differentiation of MB stem cell lines (in vitro), and the simultaneous inhibition of miRNA-Xs with Ptc1 cKO in granule cell progenitor cells induced the cancer stem cell-dominant MB (in vivo).
These results indicate that miRNA-Xs must be involved in making the hierarchy of MB cells, promising their application to eradicate the cancer stem cells for MB cure.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (13 results)

All 2015 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Deficiency of Transcription Factor Brn4 Disrupts Cochlear Gap Junction Plaques in a Model of DFN3 Non-Syndromic Deafness.2014

    • Author(s)
      Kidokoro Y, Karasawa K, Minowa O, Sugitani Y., Noda T, Ikeda K, Kamiya K.
    • Journal Title

      PLoS One.

      Volume: 9(9) Issue: 9 Pages: e108216-e108216

    • DOI

      10.1371/journal.pone.0108216

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assembly of the cochlear gap junction macromolecular complex requires connexin 26.2014

    • Author(s)
      Kamiya K, Yum SW, Kurebayashi N, Muraki M, Ogawa K, Karasawa K, Miwa A, Guo X, Gotoh S, Sugitani Y, Yamanaka H, Ito-Kawashima S, Iizuka T, Sakurai T, Noda T, Minowa O, Ikeda K.
    • Journal Title

      J Clin Invest,

      Volume: 124 Issue: 4 Pages: 1598-1607

    • DOI

      10.1172/jci67621

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assembly of the cochlear gap junction macromolecular complex requires connexin 26.2014

    • Author(s)
      Kamiya K, Yum SW, Kurebayashi N, Muraki M, Ogawa K, Karasawa K, Miwa A, Guo X, Gotoh S, Sugitani Y, Yamanaka H, Ito-Kawashima S, Iizuka T, Sakurai T, Noda T, Minowa O, Ikeda K.
    • Journal Title

      J Clin Invest.

      Volume: 124(4) Pages: 1598-1607

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radmis, a novel mitotic spindle protein that functions in cell division of neural progenitors.2013

    • Author(s)
      Yumoto T, Nakadate K, Nakamura Y, Sugitani Y, Sugitani-Yoshida R, Ueda S, Sakakibara S.
    • Journal Title

      PLoS One.

      Volume: 8(11) Issue: 11 Pages: e79895-e79895

    • DOI

      10.1371/journal.pone.0079895

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte nuclear factor 1β controls nephron tubular development.2013

    • Author(s)
      Massa F, Garbay S, Bouvier R, Sugitani Y, Noda T, Gubler MC, Heidet L, Pontoglio M, Fischer E.
    • Journal Title

      Development

      Volume: 140(4) Pages: 886-896

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] The temporal-codes of neural stem cells underlying the cell diversity and the tumorigenesis in mice.2015

    • Author(s)
      Sugitani Y., Sugitani-Yoshida R.,Yaginuma K., Nakai S., Minowa O., Ogawa O., Noda T.
    • Organizer
      第48回日本発生生物学会
    • Place of Presentation
      つくば
    • Year and Date
      2015-06-02 – 2015-06-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 大脳新皮質の細胞多様性の形成に必須なBrn転写因子の作用形式2014

    • Author(s)
      杉谷 善信、杉谷 玲子、中井 茂康、 美野輪 治、小川 正晴、野田 哲生
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular basis underlying the multi-step process in spontaneous medulloblastoma development2014

    • Author(s)
      Sugitani Y., Yaginuma K., Noda T.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] Different functional modes of Brn factors contribute to generate diverse projection neurons and glial cells in neocortex.2014

    • Author(s)
      Sugitani Y., Sugitani-Yoshida R., Nakai S., Ogawa M., Minowa O., Noda T.
    • Organizer
      Gordon Research Conference, Neural Development 2014
    • Place of Presentation
      Newport, USA
    • Year and Date
      2014-08-10 – 2014-08-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular basis underlying the multi-step process in spontaneous medulloblastoma development.2013

    • Author(s)
      Yoshinobu Sugitani, Katsuyuki Yaginuma, Tetsuo Noda
    • Organizer
      2013年度日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Related Report
      2013 Research-status Report
  • [Presentation] 2. Nmyc-targeting miRNAs provide the genetic robustness of cerebellar granule neuron differentiation against Ptc1 loss.2012

    • Author(s)
      Sugitani Y., Yaginuma K., Noda T
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] 1. Different functional modes of Brn factors contribute to generate diverse projection neuron phenotypes in neocortex.2012

    • Author(s)
      Sugitani Y., Yoshida R., Nakai S., Ogawa M., Minowa O., Noda T.
    • Organizer
      Gordon Research Conference, Neural Development 2012
    • Place of Presentation
      アメリカ ニューポート
    • Related Report
      2012 Research-status Report
  • [Presentation] Different functional modes of Brn factors contribute to generate diverse projection neuron phenotypes in neocortex.2012

    • Author(s)
      Sugitani Y., Yoshida R., Nakai S., Ogawa M., Minowa O., Noda T.
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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