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Decoding the universal cell differentiation mechanisms.

Research Project

Project/Area Number 21K20936
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0904:Internal medicine of the bio-information integration and related fields
Research InstitutionFoundation for Biomedical Research and Innovation at Kobe (2022)
Yokohama City University (2021)

Principal Investigator

Nishimura Koutarou  公益財団法人神戸医療産業都市推進機構, その他部局等, 研究員(上席・主任研究員クラス) (30909982)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords細胞分化 / 転写因子 / エピゲノム / マスター転写因子 / 普遍的細胞分化増殖停止 / p53 / ビオチン化近位標識 / 単核貪食細胞分化
Outline of Research at the Start

本研究の目的は、系譜特異的転写因子がどのように普遍的な制御因子と協調して遺伝子発現を制御しているのかをエピゲノムを中心に明らかにすることである。本研究室はIRF8により分化誘導可能な細胞株、またIRF8ノックアウト、エンハンサー欠損マウスなどを独自に樹立し、単核貪食細胞分化の研究をリードしてきた。本研究はこのIRF8細胞分化モデルにエピゲノムsgRNAライブラリーを用いたCRISPR-Cas9スクリーニング技術、また細胞内ビオチン化技術を融合し、IRF8の新たな協調因子を同定するとともに単核貪食細胞系譜のみならず普遍的細胞分化の基本原理に迫る。

Outline of Final Research Achievements

Cell differentiation is one of the unique life processes specific to eukaryotes, and its precise spatiotemporal control is essential for the development processes and maintenance of homeostasis. In recent years, epigenetics has revealed new aspects of various biological processes, which is also true for cell differentiation. In this study, we focus on the cell differentiation of hematopoietic cell lineages and the master transcription factors, aiming to elucidate unknown epigenomic regulatory mechanisms. These findings could uncover lineage-specific insights into hematopoietic cell differentiation and decode the fundamental principles of cell differentiation and aims to elucidate various disease mechanisms caused by abnormalities.

Academic Significance and Societal Importance of the Research Achievements

細胞分化を制御する転写因子や細胞表面マーカーは、個々の細胞系譜に特有のものが多く、細胞分化全体に共通のメカニズムに関する知見は乏しい。細胞分化に伴うエピゲノム制御という未だ知見に乏しい領域に注目し解析した本研究では、p53が分化に与える影響を明らかにした。この結果はあらゆる細胞系譜に共通する普遍的分化メカニズムを解明する可能性があり、生物学的にきわめて意義深いものである。また、終末分化細胞を正常に維持する分子機構の解明は、医学・医療に新たな局面を切り開く可能性があり、社会的にも非常に意義深いと考えられる。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2023 2022

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results) (of which Invited: 1 results)

  • [Journal Article] Extracellular vesicle-mediated remodeling of the bone marrow microenvironment in myeloid malignancies2023

    • Author(s)
      Hayashi Yasutaka、Nishimura Koutarou、Tanaka Atsushi、Inoue Daichi
    • Journal Title

      International Journal of Hematology

      Volume: 117 Issue: 6 Pages: 821-829

    • DOI

      10.1007/s12185-023-03587-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The early neutrophil-committed progenitors aberrantly differentiate into immunoregulatory monocytes during emergency myelopoiesis2023

    • Author(s)
      Ikeda N, Kubota H, Suzuki R, Morita M, Yoshimura A, Osada Y, Kishida K, Kitamura D, Iwata A, Yotsumoto S, Kurotaki D, Nishimura K, Nishiyama A, Tamura T, Kamatani T, Tsunoda T, Murakawa M, Asahina Y, Hayashi Y, Harada H, Harada Y, Yokota A, Hirai H, Seki T, Kuwahara M, Yamashita M, Shichino S, Tanaka M, Asano K.
    • Journal Title

      Cell Reports

      Volume: 42 Issue: 3 Pages: 112165-112165

    • DOI

      10.1016/j.celrep.2023.112165

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulated minor intron splicing in cancer.2022

    • Author(s)
      Nishimura K*, Yamazaki H*, Zang W, Inoue D.
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 9 Pages: 2934-2942

    • DOI

      10.1111/cas.15476

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Uncovering the unrecognized roles on cell fate and leukemogenesis of p53 mutations2023

    • Author(s)
      Koutarou Nishimura, Weijia Zang, Hiromi Ito, Yui Koike, Hiromi Yamazaki, Daichi Inoue
    • Organizer
      The 20th Stem Cell Research Symposium
    • Related Report
      2022 Annual Research Report
  • [Presentation] p53変異体を標的とする新規治療戦略の開発2023

    • Author(s)
      西村耕太郎、井上大地
    • Organizer
      第27回日本がん分子標的治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Dissecting the unrecognized roles of mutations in TP53 “Guardian of the Genome”2023

    • Author(s)
      Koutarou Nishimura
    • Organizer
      第82回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Revealing Unrecognized Gain-of-Function of TP53 Mutations in the Determinati on of HSC Fate2023

    • Author(s)
      Koutarou Nishimura, Weijia Zang, June Takeda, Yui Koike, Hiromi Ito, Hiromi Yamazaki, Seishi Ogawa and Daichi Inoue
    • Organizer
      第85回日本血液学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 単核貪食細胞分化におけるIrf8エンハンサー群の動的制御機構の解明2022

    • Author(s)
      西村耕太郎
    • Organizer
      第26回造血器腫瘍研究会
    • Related Report
      2021 Research-status Report

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Published: 2021-10-22   Modified: 2024-01-30  

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