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Single cell manipulation and gene expression analysis for "Singularity Biology"

Planned Research

Project AreaSingularity biology
Project/Area Number 18H05411
Research Category

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

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Shiroguchi Katsuyuki  国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (00454059)

Project Period (FY) 2018-06-29 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥98,670,000 (Direct Cost: ¥75,900,000、Indirect Cost: ¥22,770,000)
Fiscal Year 2022: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2020: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2018: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Keywords1細胞解析 / イメージング / 網羅的遺伝子発現解析 / AI / 機械学習 / 細胞分取 / 画像解析 / 細胞操作 / 遺伝子発現解析 / バイオイメージング / 一細胞解析 / シークエンシング / 深層学習 / 血液細胞 / 免疫細胞 / RNAシークエンシング / 1細胞操作 / 自動化 / 遺伝子発現 / 次世代シークエンサ
Outline of Final Research Achievements

To understand “singularity cell” or “singularity phenomena”, we developed a new technology. We first developed a multifunctional robot, the Automated Live imaging and cell Picking System (ALPS), and used it to perform single-cell RNA sequencing for microscopically observed cells. Using robotically obtained data that linked cell images and the whole transcriptome, we successfully predicted transcriptome-defined cell types and states using cell image-based deep learning. This noninvasive approach opens a new window to determine the live-cell whole transcriptome in real time. Moreover, this work, which is based on a data-driven approach, is a proof-of-concept for determining the transcriptome-defined (omics-based) phenotypes (i.e., not relying on specific genes) of any cell from cell images using a model trained on linked datasets.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した、細胞の顕微鏡画像から細胞の遺伝子発現状態を推定するアプローチは、より多くの細胞種や状態の推定・同定ができる可能性を示した。細胞を壊さずに細胞の状態を推定できるため、例えば、細胞治療に用いる細胞を移植前に評価することなどに役立つ可能性がある。基礎研究においても、細胞種の同定に用いられてきた分子マーカーが不要になる可能性があり、手順の簡易化やコストの削減になる。さらに、これまでに適切なマーカーを得ることができていない細胞種や状態の同定にも貢献すると考えられる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (34 results)

All 2022 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 10 results) Book (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 1 results)

  • [Journal Article] Robotic data acquisition with deep learning enables cell image-based prediction of transcriptomic phenotypes2022

    • Author(s)
      Jin J., Ogawa T., Hojo N., Kryukov K., Shimizu K, Ikawa T., Imanishi T., Okazaki T., Shiroguchi K
    • Journal Title

      Proc. Natl. Acad. Sci. USA.

      Volume: 120

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A circulating subset of iNKT cells mediates antitumor and antiviral immunity2022

    • Author(s)
      Cui G,,, Shiroguchi K., Ikuta K.
    • Journal Title

      Sci. Immunol.

      Volume: 7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [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] High-throughput identification and quantification of single bacterial cells in the microbiota2022

    • Author(s)
      Jin, J., Yamamoto, R., Takeuchi, T., Cui, G., Miyauchi, E., Hojo, N., Ikuta, K., Ohno, H., and Shiroguchi, K.
    • Journal Title

      Nat. Commun.

      Volume: 13 Issue: 1 Pages: 863-863

    • DOI

      10.1038/s41467-022-28426-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes2021

    • Author(s)
      Nishida Mikako、Yamashita Nahoko、Ogawa Taisaku、Koseki Keita、Warabi Eiji、Ohue Tomoyuki、Komatsu Masaaki、Matsushita Hirokazu、Kakimi Kazuhiro、Kawakami Eiryo、Shiroguchi Katsuyuki、Udono Heiichiro
    • Journal Title

      Journal for ImmunoTherapy of Cancer

      Volume: 9 Issue: 9 Pages: e002954-e002954

    • DOI

      10.1136/jitc-2021-002954

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] B cell-derived GABA elicits IL-10+ macrophages to?limit anti-tumour immunity2021

    • Author(s)
      Zhang B,Vogelzang A,Miyajima M,Sugiura Y,Wu Y,Chamoto K,Nakano R,Hatae R,Menzies RJ,Sonomura K,Hojo N,Ogawa T,Kobayashi W,Tsutsui Y,Yamamoto S,Maruya M,Narushima S,Suzuki K,Sugiya H,Murakami K,Hashimoto M,Ueno H,Kobayashi T,Ito K,Hirano T,Shiroguchi K,Matsuda F,Suematsu M,Honjo T,Fagarasan S
    • Journal Title

      Nature

      Volume: 599 Issue: 7885 Pages: 471-476

    • DOI

      10.1038/s41586-021-04082-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiomics Investigation Revealing the Characteristics of HIV-1-Infected Cells In?Vivo2020

    • Author(s)
      Aso Hirofumi、Nagaoka Shumpei、Kawakami Eiryo、Ito Jumpei、Islam Saiful、Tan Benjy Jek Yang、Nakaoka Shinji、Ashizaki Koichi、Shiroguchi Katsuyuki、Suzuki Yutaka、Satou Yorifumi、Koyanagi Yoshio、Sato Kei
    • Journal Title

      Cell Reports

      Volume: 32 Issue: 2 Pages: 107887-107887

    • DOI

      10.1016/j.celrep.2020.107887

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HaloTag-based conjugation of proteins to barcoding-oligonucleotides2020

    • Author(s)
      3.Yazaki J*, Kawashima Y, Ogawa T, Kobayashi A, Okoshi M, Watanabe T, Yoshida S, Kii I, Egami S, Amagai M, Hosoya T, Shiroguchi K, Ohara O
    • Journal Title

      Nucleic Acids Res

      Volume: 48 Issue: 2 Pages: e8-e8

    • DOI

      10.1093/nar/gkz1086

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteoprotegerin-dependent Mcell self-regulation balances gut infection and immunity.2020

    • Author(s)
      Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, KawakamiE, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, KaishoT, Iwanaga T, Hase K.
    • Journal Title

      Nat Commun

      Volume: 11 Issue: 1 Pages: 234-234

    • DOI

      10.1038/s41467-019-13883-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation2019

    • Author(s)
      Miyamoto Chizuko、Kojo Satoshi、Yamashita Motoi、Moro Kazuyo、Lacaud Georges、Shiroguchi Katsuyuki、Taniuchi Ichiro、Ebihara Takashi
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 447-447

    • DOI

      10.1038/s41467-019-08365-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] バイオDXの効果? 細胞の”顔つき”から種類・状態を捉える2022

    • Author(s)
      城口克之
    • Organizer
      第433回CBI学会講演会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Predicting cell fates by image-based machine learning for comprehensive and quantitative understanding of cell death and survival2022

    • Author(s)
      Tomoaki Okaniwa, Katsuyuki Shiroguchi
    • Organizer
      第60回日本生物物理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 実験自動化ロボットの開発と統合データ解析による 1細胞decoding2021

    • Author(s)
      城口克之
    • Organizer
      バイオDXの最前線  CRESTバイオDXキックオフシンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] An automated microscopy-based picking system for single cells which links dynamic behavior with whole gene expression2021

    • Author(s)
      Katsuyuki Shiroguchi
    • Organizer
      Pacifichem2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞動態観察・オミックス解析・機械学習を融合した 新規 1 細胞解析法の開発と免疫研究への応用2020

    • Author(s)
      城口克之
    • Organizer
      東京理科大学 総合研究院合成生物学研究部門シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] バイオイメージングとRNAシークエンシング(と機械学習)の融合による1細胞動態解析2020

    • Author(s)
      城口克之
    • Organizer
      九州大学先導物質化学研究所 非常勤講師セミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 1細胞を観て採る自動システム2020

    • Author(s)
      城口克之
    • Organizer
      Laboratory Automation Developers Conference 2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 1細胞統合解析:  ライブイメージングと 網羅的遺伝子発現解析の融合2020

    • Author(s)
      城口克之
    • Organizer
      広島県立大学 生命システム科学特別講義
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Development of an automated system to take datasets of images and sequences for the same single cells2020

    • Author(s)
      Taisaku Ogawa, Katsuyuki Shiroguchi
    • Organizer
      AGBT2020
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Linking cell dynamics and gene expression by integration of live imaging and RNA sequencing2019

    • Author(s)
      城口 克之
    • Organizer
      LSBM Symposium 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 新規手法開発により生命システムの理解へ迫る:①核酸・細胞の“デジタル”定量法の開発 ②シークエンシングとライブイメージング法の融合2019

    • Author(s)
      城口 克之
    • Organizer
      京都大学ウイルス・再生医科学研究所 セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞動態と遺伝子発現を結ぶイメージングとシークエンシングの統合解析2019

    • Author(s)
      城口 克之
    • Organizer
      第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 顕微鏡ライブイメージングと1細胞RNA-seqを組み合わせた自動化システムの開発とシンギュラリティ生物学への応用2019

    • Author(s)
      小川 泰策、城口 克之
    • Organizer
      第57回日本生物物理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 細胞動態と遺伝子発現状態を繋ぐ:顕微鏡ライブイメージングと1細胞RNAシークエンシングの融合と自動化2019

    • Author(s)
      城口 克之
    • Organizer
      第57回日本生物物理学会年会バイオフィジックスセミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Automation of live imaging, single cell picking, and sequencing system2019

    • Author(s)
      Katsuyuki Shiroguchi
    • Organizer
      ICSB2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An automated system of single cell picking and sequencing for dynamic observation of living cells2018

    • Author(s)
      城口 克之
    • Organizer
      日本生物物理学会第56回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A robotic system for combining single-cell RNA-seq with live cell imaging2018

    • Author(s)
      小川 泰策, 伊川 友活, 城口 克之
    • Organizer
      日本生物物理学会第56回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞の網羅的遺伝子発現の経時”計測”と未来予測に向けて2018

    • Author(s)
      城口 克之
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Book] DNA分子バーコード法とその新機能 バイオイノベーションに向けて ~バイテクノロジーの新技術からの新しい視点~2019

    • Author(s)
      城口克之、小川泰策
    • Total Pages
      255
    • Publisher
      シーエムシー出版
    • ISBN
      9784781314112
    • Related Report
      2018 Annual Research Report
  • [Book] 1細胞,1分子における核酸配列決定・定量技術の現状と展望2018

    • Author(s)
      城口克之
    • Total Pages
      108
    • Publisher
      科学評論社
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 核酸増幅に関する技術(仮)2022

    • Inventor(s)
      城口克之、他
    • Industrial Property Rights Holder
      理化学研究所、他
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-004729
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞操作に関する技術(仮)2020

    • Inventor(s)
      城口克之、他
    • Industrial Property Rights Holder
      理化学研究所、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 細胞搬送システム2018

    • Inventor(s)
      城口克之、他
    • Industrial Property Rights Holder
      理化学研究所、他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Acquisition Date
      2022
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞搬送システム2018

    • Inventor(s)
      城口克之、小川泰策、平藤衛
    • Industrial Property Rights Holder
      理化学研究所、ヨダカ技研(株)
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-203728
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-07-20   Modified: 2024-01-30  

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