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Principle of body malfunctioning through local cell division failure

Research Project

Project/Area Number 19KK0181
Research Category

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

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
Research InstitutionHokkaido University

Principal Investigator

Uehara Ryota  北海道大学, 先端生命科学研究院, 准教授 (20580020)

Co-Investigator(Kenkyū-buntansha) 塚田 祐基  慶應義塾大学, 理工学部(矢上), 講師 (80580000)
松尾 和哉  京都工芸繊維大学, 分子化学系, 助教 (90764952)
Project Period (FY) 2019-10-07 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords細胞分裂 / ゼブラフィッシュ / 光制御 / 染色体 / マルチスケールイメージング / 細胞骨格
Outline of Research at the Start

生体では少数細胞の分裂異常が引き金となりガンや発生障害などの疾病が惹起されるが、その原理は明らかでない。これは、生体の随意の細胞集団に分裂異常を起こし、その影響を細胞・個体レベルで追跡できる手法の欠如による。本研究では、光照射によって随意の細胞集団に局所的分裂障害を誘導できる新奇化合物と、ゼブラフィッシュ胚の個々の細胞挙動と形態形成を同時追跡できる顕微鏡システムを駆使し、分裂異常の規模に応じた子孫細胞の形質変化や組織形態・機能への影響を実験・理論の両面から解析する。この知見に基づき、分裂障害に起因する個体機能障害を回避、軽減し、病態制御に有効性をもつ介入法を予測・実証することを目指す。

Outline of Final Research Achievements

Cell division failure causes a wide range of diseases, but the quantitative relationship between the magnitude of cell division defects and their effects on the body function is unknown. In this study, we newly developed a light-responsive mitotic inhibitor. By light control using this compound, various levels of cell division defects were induced with various temporal patterns in early zebrafish embryos. We found embryos were highly resistant to one or two rounds of whole-body cell division failures during 2-4 hours post-fertilization (hpf) and to more severe mitotic failures after 5 hpf with almost intact tissue formation. Especially in the latter case, we found that the spindle checkpoint plays an important role in reducing the lethality of mitotic abnormalities.

Academic Significance and Societal Importance of the Research Achievements

本成果から、生体が甚大な分裂制御不全を経て形成された異常細胞を保持したままその機能を維持し得ることが定量的に明らかになった。疾病制御の観点からは、このような生体の許容性ががん発症などの長期的リスクを高めることが推察される。環境保全の観点では、甚大な分裂障害によるゲノム異常が長期間生体に滞留する可能性が示唆され、これが次世代へどの程度継承され生態系に作用をもちうるかの検証が必要と考えられる。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (30 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (9 results) Journal Article (12 results) (of which Int'l Joint Research: 5 results,  Open Access: 8 results,  Peer Reviewed: 10 results) Presentation (9 results) (of which Invited: 5 results)

  • [Int'l Joint Research] Indian Institute of Technology Bombay(インド)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Semmelweis University(ハンガリー)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Tata Institute of Fundamental Research/Indian Institute of Technology Bombay(インド)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Tata Institute of Fundamental Research(インド)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Semmelweis University(ハンガリー)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Tata Institute of Fundamental Research(インド)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Semmelweis University(ハンガリー)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Tata Institute for Funadamenta Research(インド)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Semmelweis University(ハンガリー)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells2024

    • Author(s)
      Ishida-Ishihara Sumire、Yaguchi Kan、Sato Kimino、Yoshizawa Koya、Miura Sena、Yang Guang、Veszelyi Krisztina、Banhegyi Gabor、Margittai Eva、Uehara Ryota
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2024.04.05.588249

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Cell shape instability during cytokinesis in tetraploid HCT116 cells2023

    • Author(s)
      Yamamoto Takahiro、Uehara Ryota
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 678 Pages: 39-44

    • DOI

      10.1016/j.bbrc.2023.08.038

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tetraploidy-linked sensitization to CENP-E inhibition in human cells.2023

    • Author(s)
      Yoshizawa Koya、Matsura Akira、Shimada Masaya、Ishida‐Ishihara Sumire、Sato Fuyu、Yamamoto Takahiro、Yaguchi Kan、Kawamoto Eiji、Kuroda Taruho、Matsuo Kazuya、Tamaoki Nobuyuki、Sakai Ryuichi、Shimada Yasuhito、Mishra Mithilesh、Uehara Ryota
    • Journal Title

      Molecular Oncology

      Volume: 10 Issue: 6 Pages: 13379-13379

    • DOI

      10.1002/1878-0261.13379

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Centrosome Loss And Cell Proliferation Defects Underlie Developmental Failure In Haploid Zebrafish Larvae2022

    • Author(s)
      Yaguchi Kan、Saito Daiki、Menon Triveni、Matsura Akira、Mizutani Takeomi、Kotani Tomoya、Nair Sreelaja、Uehara Ryota
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2022.05.12.491746

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Ultrastructural Characteristics of Finger-Like Membrane Protrusions in Cell Competition2022

    • Author(s)
      Kamasaki Tomoko、Uehara Ryota、Fujita Yasuyuki
    • Journal Title

      Microscopy

      Volume: in press Issue: 4 Pages: 195-205

    • DOI

      10.1093/jmicro/dfac017

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low-invasive 5D visualization of mitotic progression by two-photon excitation spinning-disk confocal microscopy2022

    • Author(s)
      Kamada Takafumi、Otomo Kohei、Murata Takashi、Nakata Kaito、Hiruma Shota、Uehara Ryota、Hasebe Mitsuyasu、Nemoto Tomomi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-021-04543-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular basis of functional exchangeability between ezrin and other actin-membrane associated proteins during cytokinesis2021

    • Author(s)
      Yang Guang、Hiruma Shota、Kitamura Akira、Kinjo Masataka、Mishra Mithilesh、Uehara Ryota
    • Journal Title

      Experimental Cell Research

      Volume: 403 Issue: 2 Pages: 112600-112600

    • DOI

      10.1016/j.yexcr.2021.112600

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rational design and development of a lit-active photoswitchable inhibitor targeting CENP-E2021

    • Author(s)
      Matsuo Kazuya、Tamaoki Nobuyuki
    • Journal Title

      Organic & Biomolecular Chemistry

      Volume: 19 Issue: 32 Pages: 6979-6984

    • DOI

      10.1039/d1ob01332g

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A visible light-controllable Rho kinase inhibitor based on a photochromic phenylazothiazole2021

    • Author(s)
      Matsuo Kazuya、Thayyil Sampreeth、Kawaguchi Mitsuyasu、Nakagawa Hidehiko、Tamaoki Nobuyuki
    • Journal Title

      Chemical Communications

      Volume: 57 Issue: 93 Pages: 12500-12503

    • DOI

      10.1039/d1cc04905d

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mevalonate Pathway-mediated ER Homeostasis Is Required for Haploid Stability in Human Somatic Cells2021

    • Author(s)
      Yaguchi Kan、Sato Kimino、Yoshizawa Koya、Mikami Daisuke、Yuyama Kohei、Igarashi Yasuyuki、Banhegyi Gabor、Margittai Eva、Uehara Ryota
    • Journal Title

      Cell Structure and Function

      Volume: 46 Issue: 1 Pages: 1-9

    • DOI

      10.1247/csf.20055

    • NAID

      130007988144

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Uncoupling of DNA Replication and Centrosome Duplication Cycles Is a Primary Cause of Haploid Instability in Mammalian Somatic Cells2020

    • Author(s)
      Yoshizawa Koya、Yaguchi Kan、Uehara Ryota
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 1-9

    • DOI

      10.3389/fcell.2020.00721

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Photoswitchable CENP-E Inhibitor Enabling the Dynamic Control of Chromosome Movement and Mitotic Progression2020

    • Author(s)
      Noushaba Nusrat Mafy, Kazuya Matsuo, Shota Hiruma, Ryota Uehara, Nobuyuki Tamaoki
    • Journal Title

      Journal of the American Chemical Society

      Volume: 142 Issue: 4 Pages: 1763-1767

    • DOI

      10.1021/jacs.9b12782

    • NAID

      120006955185

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] The influence of aberrant mitosis in different developmental stages in zebrafish embryos2023

    • Author(s)
      松浦暉、松尾和哉、小谷友也、玉置信之、上原亮太
    • Organizer
      第56回日本発生生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Supernumerary-centrosome dynamics and mitotic regulation in whole-genome-duplicated cells2023

    • Author(s)
      猪子雅哉、楊光、塚田祐基、上原亮太
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Developmental stage-dependent centrosome loss in haploid zebrafish larvae2023

    • Author(s)
      斎藤大輝、矢口完、Nair Sreelaja、上原亮太
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Whole-genome duplication-dependent changes in human cancer cell property in zebrafish xenografts2023

    • Author(s)
      佐藤芙由、松浦暉、石原-石田すみれ、島田康人、上原亮太
    • Organizer
      第46回日本分子生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 染色体倍加に伴う中心体の量的変化の作用2022

    • Author(s)
      上原亮太
    • Organizer
      第45回 日本分子生物学会年会ワークショップ
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 染色体倍加に伴う中心体活性亢進の原理と意義2022

    • Author(s)
      上原亮太
    • Organizer
      第95回 日本生化学会大会 シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 動物非二倍体細胞における細胞分裂障害の発生機序2021

    • Author(s)
      上原亮太
    • Organizer
      第80回 日本癌学会学術総会 シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 動物生活環を特徴づける“倍数性・中心体リンク”2021

    • Author(s)
      上原亮太
    • Organizer
      第94回日本生化学会大会 シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Ploidy-linked alterations in mitotic spindle polarity determine the long-term ploidy dynamics in mammalian cells2020

    • Author(s)
      Ryota Uehara
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2019-10-10   Modified: 2025-01-30  

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