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Transcription factor network involved in maintenance and regeneration of epithelial progenitor cells in the thymus

Research Project

Project/Area Number 21380183
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionTokyo University of Science

Principal Investigator

GOITSUKA Ryo  東京理科大学, 生命科学研究所, 教授 (50301552)

Co-Investigator(Renkei-kenkyūsha) KAWAI Yasuhiro  東京理科大学, 生命科学研究所, 助教 (00416281)
NAKAMURA Takuro  癌研究所, 発がん研究部, 部長 (00180373)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2009: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywords免疫 / 再生 / 幹細胞 / 転写制御 / 胸腺 / 転写因子 / 免疫系
Research Abstract

Most epithelial tissues retain stem/progenitor cells to maintain homeostasis of the adult tissues ; however, the existence of a thymic epithelial cell(TEC) progenitor capable of maintaining homeostasis of the postnatal thymus remains unclear. Here we show that a TEC population expressing high levels of Meis1, a homedodomain transcription factor, is enriched in non-dividing quiescent cells with an immature cellular phenotype. Postnatal inactivation of Meis1 in TECs caused exhaustion of the immature Meis1high TECs and promoted their cell cycle entry, which ultimately lead to premature disappearance of the thymus. There was an age-associated reduction in the proportion of the Meis1high TEC population, which may also relate to thymic involution. These findings indicate that in the postnatal thymus the high level expression of Meis1 marks a unique population of TECs with progenitor activity, in which Meis1 functions to maintain the undifferentiated state that is required for homeostasis of the postnatal thymus.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010 2009 Other

All Journal Article (19 results) (of which Peer Reviewed: 6 results) Presentation (22 results) Book (2 results) Remarks (1 results)

  • [Journal Article] SLP-76 is required for high affinity IgE receptor-and IL-3 receptor-mediated activation of basophils2012

    • Author(s)
      Hidano, S., Kitamura, D., Kumar, L., Geha, R. S., and Goitsuka, R.
    • Journal Title

      Int. Immunol

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatory activities2012

    • Author(s)
      Fujii, Y., Hirayama, T., Ohtake, T., Ono, N., Inoue, T., Sakurai, T., Takayama, T., Matsumoto, K., Tsukahara, N., Hidano, S., Harima, N., Nakazawa, K., Igarashi, Y., and Goitsuka, R.
    • Journal Title

      J. Immunol

      Volume: 188(1) Pages: 206-215

    • Related Report
      2011 Final Research Report
  • [Journal Article] Hypoxia induces CD133 expression in human small cell lung cancer cells by up-regulation of OCT3/4 and SOX22012

    • Author(s)
      Iida, H., Suzuki, M., Goitsuka, R., and Ueno, H.
    • Journal Title

      Int. J. Oncol

      Volume: 40(1) Pages: 71-79

    • Related Report
      2011 Final Research Report
  • [Journal Article] Lymphopenia induced by a novel selective S1P1 antagonist structurally unrelated to S1P2012

    • Author(s)
      Fujii, Y., Ohtake, H., Ono, N., Hara, T., Sakurai, T., Takahashi, S., Takayama, T., Fukasawa, Y., Shiozawa, F., Tsukahara, N., Hirayama, T., Igarashi, Y., and Goitsuka, R.
    • Journal Title

      Biochim. Biophys. Acta

      Volume: 1821(4) Pages: 600-606

    • Related Report
      2011 Final Research Report
  • [Journal Article] Blocking S1P interaction with S1P1 receptor by a novel competitive S1P1-selective antagonist inhibits angiogenesis2012

    • Author(s)
      Fujii, Y., Ueda, Y., Ohtake, H., Ono, N., Takayama, T., Nakazawa, K., Igarashi, Y. and Goitsuka, R.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 419(4) Pages: 754-760

    • Related Report
      2011 Final Research Report
  • [Journal Article] Amelioration of collagen-induced arthritis by a novel S1P1 antagonist with immunomodulatorvy activities2012

    • Author(s)
      Fujii, Y., et al
    • Journal Title

      J.Immunol.

      Volume: 188 Pages: 206-215

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphopenia induced by a novel selective S1P1 antagonist structurally unrelated to S1P2012

    • Author(s)
      Fujii, Y., et al
    • Journal Title

      Biochim.Biophys.Acta.

      Volume: 1,821 Pages: 600-606

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blocking S1P interaction with S1P1 receptor by a novel competitive a S1P1-selective antagonist inhibits angiogenesis2012

    • Author(s)
      Fujii, Y., et al
    • Journal Title

      Biochem.Biophys.Res.Commun

      Volume: 419 Pages: 754-760

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypoxia induces CD133 expression in human small cell lung cancer cells by up-regulation of OCT3/4 and SOX22012

    • Author(s)
      Iida, H., et al
    • Journal Title

      Int.J.Oncol.

      Volume: 40 Pages: 71-79

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 胸腺上皮細胞の分化と転写因子2011

    • Author(s)
      平山雄啓、後飯塚僚
    • Journal Title

      臨床免疫.アレルギー科

      Volume: 第56巻第3号 Pages: 262-268

    • Related Report
      2011 Final Research Report
  • [Journal Article] 消滅する器官としての胸腺:胸腺微小環境の形成.恒常性維持の転写制御機構2011

    • Author(s)
      後飯塚僚
    • Journal Title

      NIBS letter

      Volume: 第57巻第6号 Pages: 78-85

    • Related Report
      2011 Final Research Report
  • [Journal Article] 胸腺上皮細胞の分化と転写因子2011

    • Author(s)
      平山雄啓、後飯塚僚
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 第56巻 Pages: 262-268

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 消滅する器官としての胸腺:胸腺微小環境の形成・恒常性維持の転写制御機構2011

    • Author(s)
      後飯塚僚
    • Journal Title

      NIBS letter

      Volume: 第57巻 Pages: 78-85

    • Related Report
      2011 Annual Research Report
  • [Journal Article] SLP-76と好塩基球の活性化2010

    • Author(s)
      飛彈野真也、後飯塚僚
    • Journal Title

      臨床免疫.アレルギー科

      Volume: 54巻第2号 Pages: 155-159

    • Related Report
      2011 Final Research Report
  • [Journal Article] SLP-76と好塩基球の活性化2010

    • Author(s)
      飛弾野真也、後飯塚僚
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 54 Pages: 155-159

    • Related Report
      2010 Annual Research Report
  • [Journal Article] New approach for M-cell-specific molecules screening by comprehensive transcriptome analysis2009

    • Author(s)
      Nakato G., Fukuda S., Hase K., Goitsuka R., Cooper M. D., and Ohno H.
    • Journal Title

      DNA Res

      Volume: 16 Pages: 227-235

    • Related Report
      2011 Final Research Report
  • [Journal Article] BLNK suppresses pre-B cell leukemogenesis through inhibition of JAK32009

    • Author(s)
      Nakayama, J., Yamamoto, M., Hayashi, K., Satoh, H, . Bundo, K., Kubo, M., Goitsuka, R., Farrar, M. A, and Kitamura, D.
    • Journal Title

      Blood

      Volume: 113 Pages: 1483-1492

    • Related Report
      2011 Final Research Report
  • [Journal Article] New approach for M-cell-specific molecules screening by comprehensive transcriptome analysis2009

    • Author(s)
      Nakato G
    • Journal Title

      DNA Reserach 16

      Pages: 227-235

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BLNK suppresses pre-B cell leukemogenesis through inhibition of JAK32009

    • Author(s)
      Nakayama, J.
    • Journal Title

      Blood 113

      Pages: 1483-1492

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Subcellular localization of transcriptional coactivator Yap1, a target of the Hippo pathway, in thymic epithelial cells is regulated by interaction with thymocytes2011

    • Author(s)
      Takehiro Hirayama, Narutochi Tsukahara, and Ryo Goitsuka
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      千葉
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 未知のリガンド.レセプターシステムを介した胸腺細胞.胸腺上皮細胞間のクロストーク機構2011

    • Author(s)
      平山雄啓、後飯塚僚
    • Organizer
      第21回Kyoto T Cell Conference(KTCC)
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] 未知のリガンド・レセプターシステムを介した胸腺細胞・胸腺上皮細胞間のクロストーク機構2011

    • Author(s)
      平山雄啓
    • Organizer
      第21回Kyoto T Cell Conference (KTCC)
    • Place of Presentation
      京都
    • Related Report
      2011 Annual Research Report
  • [Presentation] 卵子形成過程におけるホメオドメイン転写因子pKnox1の発現と機能2011

    • Author(s)
      河合康洋
    • Organizer
      第104回日本繁殖学会
    • Place of Presentation
      盛岡
    • Related Report
      2011 Annual Research Report
  • [Presentation] Homeodomain transcription factor pKnox1 is required for the differentiation of spermatogonial stem cells2011

    • Author(s)
      Yasuhiro Kawai
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] マウス皮膚正常幹細胞におけるMeis1の機能解析2011

    • Author(s)
      奥村和弘
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] 消滅する免疫系器官としての胸腺:その維持と再生の制御機構(財)日本生物科学研究所2010

    • Author(s)
      後飯塚僚
    • Organizer
      第二研究会講演会
    • Place of Presentation
      青梅
    • Year and Date
      2010-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Transcription factor associated with stemness defines an epithelial progenitor cell population in the postnatal thymus2010

    • Author(s)
      Takehiro Hirayama and Ryo Goitsuka
    • Organizer
      Second Workshop of Synthetic Immunology
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Expression and function of homeodomain transcription factor Meis1 defines an epithelial progenitor cell population in the postnatal thymus2010

    • Author(s)
      Takehiro Hirayama, Takuro Nakamura, and Ryo Goitsuka
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] Expression and function of the homeodomain transcription factor pKnox1 in thymic epithelial cells2010

    • Author(s)
      Shizuka Fujii, Takehiro Hirayama, George Hollander and Ryo Goitsuka
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸
    • Related Report
      2011 Final Research Report
  • [Presentation] 成体胸腺微小環境の維持におけるホメオボックス転写因子Meis1の役割2010

    • Author(s)
      平山雄啓
    • Organizer
      第21回Kyoto T Cell Conference(KTCC)
    • Place of Presentation
      柴蘭会館(京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expression and function of homeodomain transcription factor Meis1 defines an epithelial progenitor cell population in the postnatal thymus2010

    • Author(s)
      Takehiro Hirayama
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expression and function of the homeodomain transcription factor pKnox in thymic epithelial cells2010

    • Author(s)
      Shizuka Fujii
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expression and function of the homeodomain transcription factor Meis1 in dendritic cell development2010

    • Author(s)
      Takafumi Ohtsuka
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2010 Annual Research Report
  • [Presentation] SLP-76 is regulated for IL-3 receptor-induced IL-4 production of basophils2010

    • Author(s)
      Shinya Hidano
    • Organizer
      The 14^<th> International Congress of Immunology
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2010 Annual Research Report
  • [Presentation] THE TRANSCRIPTION FACTOR ASSOCIATED WITH STEMNESS DEFINES AN EPITHELIAL PROGENITOR CELL POPULATION IN THE POSTNATAL THYMUS2010

    • Author(s)
      Ryo Goitsuka
    • Organizer
      The Second Workshop of Synthetic Immunology
    • Place of Presentation
      柴蘭会館(京都)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Meis1 is essential for the maintenance of postnatal thymic epithelial progenitor cells2009

    • Author(s)
      Takehiro Hirayama and Ryo Goitsuka
    • Organizer
      第39回日本免疫学会総会・学術集会
    • Place of Presentation
      大阪
    • Related Report
      2011 Final Research Report
  • [Presentation] Meis1 deficiency impairs the postnatal thymic microenvironment to induce early thymic involution2009

    • Author(s)
      Takehiro Hirayama, and Ryo Goitsuka
    • Organizer
      The 5^<th> International Workshop of Kyoto T cell Conference
    • Place of Presentation
      京都
    • Related Report
      2011 Final Research Report
  • [Presentation] Meis1 deficiency impairs the postnatal thymic microenvironment to induce early thymic involution2009

    • Author(s)
      Takehiro Hirayama
    • Organizer
      The 5^<th> International Workshop of Kyoto T cell Conference 2009
    • Place of Presentation
      柴蘭会館(京都)
    • Related Report
      2009 Annual Research Report
  • [Presentation] The role of Cebp-beta in PreB-ALL and cooperation with Bash mutation2009

    • Author(s)
      Morito Kurata
    • Organizer
      第68回 日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2009 Annual Research Report
  • [Presentation] The role of Meis1 in MLL-ENL-induced AML2009

    • Author(s)
      Yuichi Wakabayashi
    • Organizer
      第68回 日本癌学会学術集会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2009 Annual Research Report
  • [Presentation] Meis1 is essential for the maintenance of postnatal thymic epithelial progenitor cells2009

    • Author(s)
      Takehiro Hirayama
    • Organizer
      第39回 日本免疫学会総会・学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Related Report
      2009 Annual Research Report
  • [Book] アレルギー疾患イラストレイテッド第2版2010

    • Author(s)
      後飯塚僚
    • Publisher
      メディカルレビュー社
    • Related Report
      2011 Final Research Report
  • [Book] アレルギー疾患イラストレイテッド 第2版2010

    • Author(s)
      後飯塚僚
    • Total Pages
      304
    • Publisher
      (株)メディカルレビュー社
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.rs.noda.sut.ac.jp/.ribsjm/indexj.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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