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Roles of a non-coding RNA that regulates normal and neoplastic T cell development

Research Project

Project/Area Number 19KK0222
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionTokyo University of Science

Principal Investigator

Ikawa Tomokatsu  東京理科大学, 研究推進機構生命医科学研究所, 教授 (60450392)

Co-Investigator(Kenkyū-buntansha) 高野 淳一朗  国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (00852162)
磯田 健志  東京医科歯科大学, 医学部附属病院, 助教 (80815225)
Project Period (FY) 2019-10-07 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords非コードRNA / T細胞分化 / 胸腺 / エピジェネティクス / 転写因子 / 白血病 / 転写制御 / がん化
Outline of Research at the Start

T細胞は感染防御だけでなく、がん、アレルギー、生活習慣病など多くの疾患に関わる。T細胞がその機能を発揮するためには分化過程において細胞の運命が厳格に制御されなければならない。これは様々な転写調節因子によって制御されているが、詳細は明らかでない。申請者らは以前、転写因子Bcl11bがT細胞分化に必須であることを報告した。さらにBcl11bのエンハンサー領域から転写される非コードRNA(ThymoD)を発見し、これがT細胞の運命制御に重要であることを示した。ThymoD欠損マウスではT細胞性白血病を発症する。そこで本研究では、ThymoDによるT細胞分化および白血病抑制機構を解明することを目指す。

Outline of Final Research Achievements

Non-coding RNA is involved in various life phenomena, whereas the molecular mechanism is largely unknown. We focused on the role of ThymoD, which is a non-coding RNA exclusively expressed in the thymus. We generated the induced Leukocyte Stem (iLS) cells from bone marrow of ThymoD-deficient mice. The ThymoD-deficient iLS cells fail to differentiate into T cells and express Bcl11b, suggesting that the ThymoD is critical for the expression of Bcl11b and further T cell differentiation. On the other hand, we identified the human ThymoD-BCL11B locus in normal and malignant T cells for the first time in the world. The blockade of the transcription of human ThymoD affected the epigentic modification of BLC11B loci, suggesting that the ThymoD is essential for both mouse and human T cell development.

Academic Significance and Societal Importance of the Research Achievements

我々は機能が不明なノンコーティングRNA(ThymoD)に着目し、ThymoDのT細胞分化における役割を解析した。その結果、ThymoDがT細胞の分化や腫瘍化に重要であることが明らかとなった。また、ThymoDはヒト正常T細胞やT細胞性白血病細胞にも発現し機能的であることを世界で初めて発見した。これにより、ThymoDを標的とした白血病の新規治療法の開発に結びつくことが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (27 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (15 results) (of which Int'l Joint Research: 6 results,  Invited: 6 results)

  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of California, San Diego(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Oxford(英国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Different cell imaging methods did not significantly improve immune cell image classification performance2022

    • Author(s)
      Ogawa T, Ochian K, Iwata T, Ikawa T, Tsuzuki T, Shiroguchi K and Takahashi K.
    • Journal Title

      Plos One

      Volume: 17 Issue: 1 Pages: e0262397-e0262397

    • DOI

      10.1371/journal.pone.0262397

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 転写因子とマクロファージ分化2021

    • Author(s)
      伊川 友活
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 75 Pages: 699-706

    • NAID

      40022604514

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 転写因子とマクロファージ分化2021

    • Author(s)
      Ikawa-T
    • Journal Title

      臨床免疫・アレルギー科

      Volume: -

    • NAID

      40022604514

    • Related Report
      2020 Research-status Report
  • [Journal Article] Chromatin Protein PC4 Orchestrates B Cell Differentiation by Collaborating with IKAROS and IRF42020

    • Author(s)
      Ochiai Kyoko、Yamaoka Mari、Swaminathan Amrutha、Shima Hiroki、Hiura Hitoshi、Matsumoto Mitsuyo、Kurotaki Daisuke、Nakabayashi Jun、Funayama Ryo、Nakayama Keiko、Arima Takahiro、Ikawa Tomokatsu、Tamura Tomohiko、Sciammas Roger、Bouvet Philippe、Kundu Tapas K.、Igarashi Kazuhiko
    • Journal Title

      Cell Reports

      Volume: 33 Issue: 12 Pages: 108517-108517

    • DOI

      10.1016/j.celrep.2020.108517

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL2020

    • Author(s)
      Atsushi Watanabe, Kunio Miyake, Jessica Nordlund, Ann-Christine Syvanen, Louise van der Weyden, Hiroaki Honda, Norimasa Yamasaki, Akiko Nagamachi, Toshiya Inaba, Tomokatsu Ikawa, Kevin Y Urayama, Nobutaka Kiyokawa, Akira Ohara, Shunsuke Kimura, Yasuo Kubota, Junko Takita, Hiroaki Goto, Kimiyoshi Sakaguchi, et al.
    • Journal Title

      Blood

      Volume: 136 Issue: 20 Pages: 2319-2333

    • DOI

      10.1182/blood.2019004090

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell fate decisions: The role of transcription factors in early B-cell development and leukemia.2020

    • Author(s)
      Fischer U, Yang JJ, Ikawa T, Hein D, Vicente-Duenas, Borkhardt A and Sanchez-Garcia I.
    • Journal Title

      Blood Cancer Discov

      Volume: 1 Issue: 3 Pages: 224-233

    • DOI

      10.1158/2643-3230.bcd-20-0011

    • Related Report
      2020 Research-status Report
  • [Journal Article] Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians2019

    • Author(s)
      Hashimoto K, Kouno T, Ikawa T, Hayatsu N, Miyajima Y, Yabukami H, Terooatea T, Sasaki T, Suzuki T, Valentine M, Pascarella G, Minoda A, Taniuchi I, Arai Y, Hirose N, Carninci P
    • Journal Title

      PNAS

      Volume: 116 Issue: 48 Pages: 24242-24251

    • DOI

      10.1073/pnas.1907883116

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] B細胞分化を駆動する転写プログラムとクロマチン制御2019

    • Author(s)
      薬師寺 那由多, 伊川 友活
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 71 Pages: 215-222

    • Related Report
      2019 Research-status Report
  • [Presentation] 急性リンパ性白血病モデルを用いた発症メカニズムの解明2021

    • Author(s)
      伊川 友活
    • Organizer
      第85回日本インターフェロン・サイトカイン学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Polycomb Group protein PCGF1 links hematopoietic lineage specification with DNA replication2021

    • Author(s)
      Tomokatsu Ikawa, Junichiro Takano, Koseki Haruhiko
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 人工白血球幹(iLS)細胞を用いたTCF3融合遺伝子陽性B-ALL発症モデルの確立2021

    • Author(s)
      重廣司、鈴木藍彩、Gu Fangbing、平川真弓、高木正稔、犬飼岳史、伊川友活
    • Organizer
      第83回日本血液学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 人工白血球幹(iLS)細胞を用いた、TCF3融合型B細胞性急性リンパ性白血病の発症機序の解明2021

    • Author(s)
      鈴木藍彩、重廣司、伊川友活
    • Organizer
      第30回Kyoto T Cell Conference
    • Related Report
      2021 Annual Research Report
  • [Presentation] Molecular processes of TCF3-fusio type B-ALL development revealed by a newly-established mouse model2021

    • Author(s)
      Aisa Suzuki and Tomokatsu Ikawa
    • Organizer
      第50回日本免疫学会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transcriptional regulation that determines early lymphocyte development and leukemia2020

    • Author(s)
      Ikawa T
    • Organizer
      The 7th Cancer Epigenetics Symposium
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 免疫細胞の分化・腫瘍化を制御するエピジェネティクス2020

    • Author(s)
      伊川 友活
    • Organizer
      第105回日本栄養・食料学会関東支部大会シンポジウム
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] ポリコームタンパクPCGF1は造血系細胞分化においてDNA複製と運命制御を結びつける働きをしている2020

    • Author(s)
      伊川 友活
    • Organizer
      さきがけ第4回終了領域研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Non-canonical PRC1.1 is required for specification of hematopoietic progenitor cells toward B lymphoid lineage2019

    • Author(s)
      Takano J, Ito S, Nakajima-Takagi Y, Iwama A, Ikawa T and Koseki H
    • Organizer
      第13回日本エピジェネティクス研究会年会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 異性型ポリコームタンパクPCGF1はPRC2の機能を安定化させることによりB 細胞系列への運命決定を促進している2019

    • Author(s)
      伊川 友活, 高野 淳一郎, 古関 明彦
    • Organizer
      第29回Kyoto T cell Conference
    • Related Report
      2019 Research-status Report
  • [Presentation] Essential roles of variant PCGF1-PRC1 n regulating hematopoietic cell fates2019

    • Author(s)
      Ikawa T and Takano J
    • Organizer
      FASEB The Molecular Mechanisms of Immune Cell Development and Function Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 無限に増幅する血液前駆細胞を用いた抗腫瘍薬の開発2019

    • Author(s)
      伊川 友活
    • Organizer
      BioJapan2019
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Variant PCGF1-PRC1 regulates hematopoietic cell fates through nucleosome composition2019

    • Author(s)
      Takano J, Ito S, Nakajima-Takagi Y, Iwama A, Koseki H, and Ikawa T
    • Organizer
      第81回日本血液学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Epigenetic control in early lymphocyte development2019

    • Author(s)
      Ikawa T
    • Organizer
      The 30th Anniversary International Symposium of Research Institute for Biomedical Sciences
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Essential roles of PCGF1 in controlling hematopoietic cell fates2019

    • Author(s)
      Ikawa T , Takano J, and Koseki H
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-10-10   Modified: 2023-01-30  

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