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miRNAはB細胞運命決定において転写因子を超えられるか?

Publicly Offered Research

Project AreaMolecular mechanisms of cell fate determination in the cells that undergo stepwise differentiation to multiple pathways
Project/Area Number 25118726
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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

Principal Investigator

幸谷 愛  東海大学, 医学部, 准教授 (00517477)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞運命 / B細胞 / miRNA / 転写因子 / EBF1 / 細胞運命制御
Outline of Annual Research Achievements

細胞運命決定は発生、成体組織の維持において重要である。古典的細胞運命決定には転写因子が必須であると考えられてきたが、我々はこの古典的概念を覆す現象を発見した。(Okuyama et al PNAS 2013, Cold Splring HarborMeeting 2014 Oral presentation, ASH 2013 Oral presentation)きっかけは白血病細胞にmiRNAを導入した際に、B細胞分化を誘導できたにもかかわらず、B細胞分化に必須の転写因子であるE2A, EBF1, PAX5の発現上昇を全く認めなかったことにある。この現象から、miRNAが転写因子独立にB細胞分化を引き起こす可能性を検討するために、3つの転写因子の中でも、その機能が他を補完するEBF1に着目した。B細胞運命決定に必須転写因子EBF1を欠損させた場合、B細胞系列が欠損する。B細胞が最終段階まで分化した状態の細胞においてさえ、EBF1を欠損させると全てのB細胞がT細胞、ILC細胞に運命転換をする。 (Nature Immunology 2013)このようにB細胞をB細胞たらしめるのが転写因子EBF1を欠損した造血前駆細胞にたった一つのmiRNA, miR-195を導入すると、B細胞系列決定が起こった。EBF1欠損造血前駆細胞にmiR-195を導入し、IL-7, Flt3, 存在下ストローマ細胞Tst4上で2週間培養すると、B細胞系列決定を示す表面マーカーCD19が発現,分子学的マーカーVDJ領域の組み換えが認められた。これらのマーカはB細胞系列決定が引き起こされたことを示し、本研究課題の目的が達成された。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (17 results)

All 2014 2013 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (5 results) (of which Invited: 4 results) Remarks (2 results)

  • [Journal Article] Novel functional small RNAs are selectively loaded onto mammalian Ago12014

    • Author(s)
      Yamakawa, N. Okuyama, K. Ogata, J. Kanai, A. Helwak, A. Takamatsu, M. Imadome, K. I. Takakura, K. Chanda, B. Kurosaki, N. Yamamoto, H. Ando, K. Matsui, H. Inaba, T. Kotani, A.
    • Journal Title

      Nucleic Acids Res

      Volume: 未確定 Issue: 8 Pages: 5289-5301

    • DOI

      10.1093/nar/gku137

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Small RNA as a regulator of hematopoietic development, immune response in infection and tumorigenesis2014

    • Author(s)
      Okuyama K, Ogata J, Yamakawa N, Chanda B, Kotani A.
    • Journal Title

      International Journal of Hematology

      Volume: 99 Issue: 5 Pages: 553-60

    • DOI

      10.1007/s12185-014-1564-4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guest editorial :noncoding RNA in RNA hematopoietic system2014

    • Author(s)
      Kotani A
    • Journal Title

      International Journal of Hematology

      Volume: 99 Issue: 5 Pages: 529-30

    • DOI

      10.1007/s12185-014-1574-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic mutator Activation-induced cytidine deaminase (AID) as a therapeutic target2014

    • Author(s)
      Kotani A
    • Journal Title

      Rinsho Ketsueki

      Volume: 55 Issue: 7 Pages: 780-784

    • DOI

      10.11406/rinketsu.55.780

    • NAID

      130004678954

    • ISSN
      0485-1439, 1882-0824
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of tumor-derived secretary small RNAs in EBV related lymphoma2014

    • Author(s)
      Kotani A
    • Journal Title

      Uirusu

      Volume: 64 Issue: 1 Pages: 43-48

    • DOI

      10.2222/jsv.64.43

    • NAID

      130004922977

    • ISSN
      0042-6857, 1884-3433
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel functional small RNAs are selectively loaded onto mammalian Ago1.2014

    • Author(s)
      Yamakawa N, Okuyama K, Ogata J, Kanai A, Helwak A, Takamatsu M, Imadome KI, Takakura K, Chanda B, Kurosaki N, Yamamoto H, Ando K, Matsui H, Inaba T, Kotani A.
    • Journal Title

      Nucleic Acids Res.

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small RNA as a regulator of hematopoietic development, immune response in infection and tumorigenesis.2014

    • Author(s)
      Okuyama K, Ogata J, Yamakawa N, Chanda B, Kotani A.
    • Journal Title

      Int J Hematol

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guest editorial: noncoding RNA in hematopoietic system.2014

    • Author(s)
      Kotani A
    • Journal Title

      Int J Hematol

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-126-mediated control of cell fate in B cell-myeloid progenitors as a potential alternative to transcriptional factors *corresponding author2013

    • Author(s)
      Kazuki Okuyama, Tomokatsu Ikawa, Bernhard Gentner, Katsuto Hozumi, Ratanakanit Harnprasopwat, Jun Lu, Riu Yamashita, Daon Ha, Takae Toyoshima, Bidisha Chanda, Toyotaka Kawamata, Kazuaki Yokoyama, Shusheng Wang, Kiyoshi Ando, Harvey F. Lodish, Arinobu Tojo, Hiroshi Kawamoto, and Ai Kotani*
    • Journal Title

      Proc Natl Acad Sci U. S.A.

      Volume: 110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivo leukemogenic potential of an interleukin 7 receptor α chain mutant in hematopoietic stem and progenitor cells.2013

    • Author(s)
      Yokoyama K, Yokoyama N, Izawa K, Kotani A, Harashima A, Hozumi K, Tojo A.
    • Journal Title

      BLOOD

      Volume: 122

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] A single micro-RNA can completely rescue B-cell differentiation2014

    • Author(s)
      Bidisha Chanda, Tomokatsu Ikawa, Kazuki Okuyama, Katsuto Hozumi, Hiroshi Kawamoto, Ai Kotani
    • Organizer
      Cold Spring Harber Meeting
    • Place of Presentation
      New York
    • Related Report
      2013 Annual Research Report
  • [Presentation] miRNAは転写因子をこえられるか2013

    • Author(s)
      幸谷 愛
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 治療標的としてのAID2013

    • Author(s)
      幸谷 愛
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 腫瘍由来分泌性小分子RNAによる炎症性ニッチの制御2013

    • Author(s)
      幸谷 愛
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] EBV関連リンパ腫から放出される分泌性EBVコード小分子RNAの炎症性ニッチ形成における役割"2013

    • Author(s)
      幸谷 愛
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Remarks] 幸谷研究室

    • URL

      http://kotani.med.u-tokai.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 幸谷研究室

    • URL

      http://kotani.med.u-tokai.ac.jp/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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