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Development of whole-organ 3D staining method for the analysis of protein expression, modification, and activity

Research Project

Project/Area Number 19H03413
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionJuntendo University (2021)
The University of Tokyo (2019-2020)

Principal Investigator

Etsuo Susaki  順天堂大学, 大学院医学研究科, 教授 (10444803)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords3次元組織学 / 組織透明化 / 3次元イメージング / セルオミクス
Outline of Research at the Start

3次元組織学は未だ適応範囲が限定的であるため、研究代表者は理想的な抗体・染色剤の組織内浸透条件を探索し、大型組織サンプルを高効率に3次元染色・観察する新しいプロトコルの構築を進めている。本研究課題では、この3次元組織学技術を発展させ、全身のあらゆる臓器を対象とした臓器スケール・細胞解像度の多色3次元染色・観察技術を確立することを目的とする。特に、本技術が核酸ではなくタンパク質を検出対象とできる利点を生かし、リン酸化などの翻訳後修飾や酵素活性を臓器スケール・細胞解像度で評価する新たな技術の確立を目的とする。

Outline of Final Research Achievements

The purpose of this research was to establish an original organ-scale multicolor 3D staining and observation technique. During the research, we invented a new, high-performance tissue 3D staining protocol named CUBIC-HistoVIsion (CUBIC-HV) based on our finding that the biological tissue can be defined as a kind of gel. The published paper gathered worldwide attention and was selected as one of the 2020 Top 50 Life and Biological Sciences Articles in the journal. We also conducted many collaboration research by using the newly developed technology.

Academic Significance and Societal Importance of the Research Achievements

本研究課題は、世界最高性能の3次元組織学技術を確立するとともに、組織内のタンパク質の状態を網羅的に解析する新しい研究アプローチの確立に貢献した。この方法は、創薬や臨床病理学を始めとする、基礎研究以外の様々な分野での活用が期待され、実際に応用も進められている。

Report

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

    (47 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 7 results) Presentation (21 results) (of which Int'l Joint Research: 4 results,  Invited: 18 results) Book (3 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] RWTH Aachen University/RFW University of Bonn/Univ. Med. Cent. Hamburg-Eppendorf(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Development and perspective of cell-omics technology2022

    • Author(s)
      洲崎悦生
    • Journal Title

      生化学

      Volume: 94 Issue: 1 Pages: 26-36

    • DOI

      10.14952/SEIKAGAKU.2022.940026

    • ISSN
      0037-1017
    • Year and Date
      2022-02-25
    • Related Report
      2021 Annual Research Report
  • [Journal Article] 組織透明化技術の原理と応用2022

    • Author(s)
      洲崎悦生
    • Journal Title

      TCIメール

      Volume: 189 Pages: 10-17

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 実用的な全臓器3次元染色技術のボトムアップ設計2022

    • Author(s)
      洲崎悦生
    • Journal Title

      月刊臨床免疫・アレルギー科

      Volume: 77 Pages: 239-243

    • Related Report
      2021 Annual Research Report
  • [Journal Article] CUBIC-Cloud provides an integrative computational framework toward community-driven whole-mouse-brain mapping2021

    • Author(s)
      Mano T, Murata K, Kon K, Shimizu C, Ono H, Shi S, Yamada RG, Miyamichi K, Susaki EA, Touhara K, Ueda HR.
    • Journal Title

      Cell Reports Methods

      Volume: 1 Issue: 2 Pages: 100038-100038

    • DOI

      10.1016/j.crmeth.2021.100038

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of Sympathetic Signaling in Macrophages Blocks Systemic Inflammation and Protects against Renal Ischemia-Reperfusion Injury2021

    • Author(s)
      Hasegawa S, Inoue T, Nakamura Y, Fukaya D, Uni R, Wu CH, Fujii R, Peerapanyasut W, Taguchi A, Kohro T, Yamada S, Katagiri M, Ko T, Nomura S, Nakanishi Ozeki A, Susaki EA, Ueda HR, Akimitsu N, Wada Y, Komuro I, Nangaku M, Inagi R.
    • Journal Title

      J Am Soc Nephrol.

      Volume: - Issue: 7 Pages: 1599-1615

    • DOI

      10.1681/asn.2020121723

    • NAID

      120007174517

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 新規技術が駆動するがん微小環境の理解 1.高精度のがん診断に向けた3次元組織病理学の現在と未来2021

    • Author(s)
      洲崎悦生
    • Journal Title

      実験医学増刊:がん微小環境に1細胞レベルで挑む

      Volume: 39 Pages: 174-178

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16high Cells In Vivo.2020

    • Author(s)
      Omori S, Wang TW, Johmura Y, ..., Sakamoto T (15番目), ..., Nakanishi M.
    • Journal Title

      Cell Metab

      Volume: 32 Issue: 5 Pages: 814-828

    • DOI

      10.1016/j.cmet.2020.09.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues2020

    • Author(s)
      Susaki Etsuo A.、Shimizu Chika、Kuno Akihiro、Tainaka Kazuki、Li Xiang、Shibayama Mitsuhiro、Ueda Hiroki R. et al.
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1 Pages: 1982-1982

    • DOI

      10.1038/s41467-020-15906-5

    • NAID

      120006956725

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 腎臓を視る 組織透明化による腎臓病の3次元病態解析2020

    • Author(s)
      長谷川 頌, 洲崎 悦生, 上田 泰己, 南学 正臣
    • Journal Title

      生化学

      Volume: 92 Pages: 838-843

    • NAID

      40022454310

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 【単一細胞レベル解析の新技術】組織・個体の全細胞解析の最前線2020

    • Author(s)
      洲崎 悦生
    • Journal Title

      細胞

      Volume: 52 Pages: 728-732

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Visualization and molecular characterization of whole-brain vascular networks with capillary resolution.2020

    • Author(s)
      Takeyuki Miyawaki,Shota Morikawa,Etsuo A Susaki,Ai Nakashima,Haruki Takeuchi,Shun Yamaguchi,Hiroki R Ueda,Yuji Ikegaya
    • Journal Title

      Nature communications

      Volume: 11 Issue: 1 Pages: 1104-1104

    • DOI

      10.1038/s41467-020-14786-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The oral hypoxia-inducible factor prolyl hydroxylase inhibitor enarodustat counteracts alterations in renal energy metabolism in the early stages of diabetic kidney disease2019

    • Author(s)
      Hasegawa Sho、Tanaka Tetsuhiro、Saito Tomoyuki、Fukui Kenji、Wakashima Takeshi、Susaki Etsuo A.、Ueda Hiroki R.、Nangaku Masaomi
    • Journal Title

      Kidney International

      Volume: in press Issue: 5 Pages: 934-950

    • DOI

      10.1016/j.kint.2019.12.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis2019

    • Author(s)
      Puelles VG, Fleck D, Ortz L, Papadouri S, Thiago T, Boehner A, van der Wolde JW, Vogt M, Saritas T, Kuppe C, Fuss A, Menzel S, Klinkhammer BM, Mller-Newen G, Heymann F, Decker L, Braun F, Kretz O, Huber TB, Susaki EA, Ueda HR, et al.
    • Journal Title

      Kidney international

      Volume: AOP Issue: 2 Pages: 505-516

    • DOI

      10.1016/j.kint.2019.02.034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comprehensive three-dimensional analysis (CUBIC-kidney) visualizes abnormal renal sympathetic nerves after ischemia/reperfusion injury.2019

    • Author(s)
      Hasegawa S, Susaki EA, Tanaka T, Komaba H, Wada T, Fukagawa M, Ueda HR, Nangaku M
    • Journal Title

      Kidney international

      Volume: AOP Issue: 1 Pages: 129-138

    • DOI

      10.1016/j.kint.2019.02.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 【バイオマテリアル研究に役立つ分析技術・評価法】生体組織の透明化とイメージング技術2019

    • Author(s)
      吉田 将太,松本 桂彦,洲崎 悦生,上田 泰己
    • Journal Title

      バイオマテリアル-生体材料-

      Volume: 37 Pages: 264-269

    • Related Report
      2019 Annual Research Report
  • [Journal Article] CUBICを用いた組織透明化と3次元観察2019

    • Author(s)
      洲崎悦生
    • Journal Title

      和光純薬時報

      Volume: 87 Pages: 16-19

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 人工知能と神経科学 病理画像の自動診断技術と3次元病理学の発展2019

    • Author(s)
      洲崎悦生
    • Journal Title

      Brain and Nerve

      Volume: 71

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 透明イメージングの臨床応用 組織透明化技術と細胞ラベリング技術2019

    • Author(s)
      洲崎悦生
    • Journal Title

      月刊メディカル・サイエンス・ダイジェスト

      Volume: 45

    • Related Report
      2019 Annual Research Report
  • [Presentation] CUBIC for whole-organ/body cell circuit and tissue architecture analysis.2021

    • Author(s)
      洲崎悦生
    • Organizer
      1st mesoSPIM User Meeting
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 神経科学における組織透明化技術の活用2021

    • Author(s)
      洲崎悦生
    • Organizer
      環境医学研究所 ・ 順天堂かゆみ研究センター 第7回学術シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CUBIC-HistoVIsion:臓器・全身をカバーする3次元組織学の実現2021

    • Author(s)
      洲崎悦生
    • Organizer
      第94回日本生化学大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CUBIC-HistoVIsion realizes whole-organ/body three-dimensional histology2021

    • Author(s)
      洲崎悦生
    • Organizer
      第30回日本バイオイメージング学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Approaching the multicellular systems by cell-omics technology2021

    • Author(s)
      Etsuo A. Susaki
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] CUBIC-HistoVIsion: a versatile three-dimensional whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissue (Keynote talk)2020

    • Author(s)
      Etsuo A. Susaki
    • Organizer
      Volume Imaging Symposium (VIS) 2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] セルオミクスによる細胞ネットワークの定量的解析2020

    • Author(s)
      洲崎悦生
    • Organizer
      第5回理論免疫学ワークショップ
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多細胞システムの理解に向けた セルオミクス技術の開発と応用2020

    • Author(s)
      洲崎悦生
    • Organizer
      第3回 ExCELLSシンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] CUBIC-HistoVIsion: a versatile three-dimensional whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissue2020

    • Author(s)
      洲崎悦生
    • Organizer
      4th NanoLSI Symposium, WPI Kanazawa University
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 多細胞システムの理解に向けたセルオミクス技術の開発と応用2020

    • Author(s)
      洲崎悦生
    • Organizer
      Cell Biology, Developmental Biology, and Systems Biology course meeting (Webiner)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多細胞体をシステムとして理解するアイデアと方法2020

    • Author(s)
      洲崎悦生
    • Organizer
      岡山大学医学部 特別講義
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 細胞ネットワークの網羅的解析-個体をシステムとして理解するアイデアと方法2020

    • Author(s)
      洲崎悦生
    • Organizer
      順天堂大学医学部 医学研究入門II 特別講義
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] セルオミクス技術の開発と医学生物学応用2020

    • Author(s)
      洲崎悦生
    • Organizer
      2020年日本バイオインフォマティクス学会年会 第9回生命医薬情報学連合大会2020
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Versatile 3D whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissue2020

    • Author(s)
      Etsuo A. Susaki
    • Organizer
      Webinar at Washington University (hosted by Dr. Adam Glaser)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] CUBIC-HV 組織透明化と組み合わせて使用できる新しい3次元染色技術2020

    • Author(s)
      洲崎悦生
    • Organizer
      東京化成工業 ウェビナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] セルオミクスによる多細胞システム解明へのアプローチ2019

    • Author(s)
      洲崎悦生
    • Organizer
      岡山大学次世代研究拠点シンポジウム2020「口腔器官の再構築から器官の発生・再生の統一原理の解明」
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A versatile three-dimensional whole-organ/body staining and imaging with single-cell resolution based on electrolyte-gel properties of biological tissue2019

    • Author(s)
      洲崎悦生
    • Organizer
      The Light Sheet Microscopy Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A versatile protocol for three-dimensional whole-organ/body staining and imaging with single-cell resolution based on electrolyte-gel properties of biological tissue.2019

    • Author(s)
      Susaki EA et al.
    • Organizer
      Society for Neuroscience 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織透明化技術の開発と医学生物学応用(モーニングレクチャー)2019

    • Author(s)
      洲崎悦生
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 全臓器・全身スケールの多階層空間オミクス実現に向けたアプローチ2019

    • Author(s)
      洲崎悦生
    • Organizer
      シングルセルゲノミクス研究会2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 全臓器・全身の細胞ダイバーシティー解明を目指す臓器スケール3次元組織学への挑戦2019

    • Author(s)
      洲崎悦生
    • 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 合同年次大会 共催シンポジウム「総力戦でのぞむ細胞社会ダイバーシティー解明への挑戦」(兼オーガナイザー)
    • Related Report
      2019 Annual Research Report
  • [Book] Handbook of Tissue Optical Clearing - New Prospects in Optical Imaging.2021

    • Author(s)
      Etsuo A. Susaki, Hiroki R. Ueda (Editors: Dan Zhu, Elina A. Genina, Valery V. Tuchin)
    • Total Pages
      682
    • Publisher
      CRC Press
    • ISBN
      9781000466300
    • Related Report
      2021 Annual Research Report
  • [Book] 医用工学ハンドブック2021

    • Author(s)
      洲崎悦生(佐久間一郎、秋吉一成、津本, 浩平 編)
    • Total Pages
      475
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437350
    • Related Report
      2021 Annual Research Report
  • [Book] 先端の分析法 第2版2021

    • Author(s)
      洲崎悦生(小澤岳昌、北森武彦、中村洋、藤浪眞紀、宮村一夫 編)
    • Total Pages
      973
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860437374
    • Related Report
      2021 Annual Research Report
  • [Remarks] 脳の全細胞を解析するクラウドシステムの開発

    • URL

      https://www.riken.jp/press/2021/20210622_1/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 3次元組織学による全臓器・全身の観察技術を確立

    • URL

      https://www.riken.jp/press/2020/20200427_2/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 世界初、体内に存在する老化の原因となる細胞の解析に成功

    • URL

      https://www.ims.u-tokyo.ac.jp/imsut/jp/about/press/page_00033.html

    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 生体組織染色試薬、生体組織染色キット及び生体組織染色方法2019

    • Inventor(s)
      洲崎悦生、上田泰己
    • Industrial Property Rights Holder
      株式会社CUBICStars
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-157984
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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