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Advanced 3D neuropathology based on whole-mount tissue staining methods

Research Project

Project/Area Number 18H02105
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionNiigata University

Principal Investigator

Tainaka Kazuki  新潟大学, 脳研究所, 教授 (80506113)

Project Period (FY) 2018-04-01 – 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: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords透明化 / 3Dイメージング / 神経病理 / ケミカルプローブ
Outline of Final Research Achievements

Current biopsy and histology have long relied on thin-sectioned 2D images with several chemical staining methods and specific immunohistochemistry. Facile 3D visualization of human brain tissue with single-cell resolution would provide a novel concept of the neuropathological diagnosis and contribute our understanding of pathological mechanisms based on comprehensive and quantitative analysis of individual biomarker. In this project, we aimed at establishing a novel 3D neuropathology by developing highly efficient clearing and staining protocol for human brain tissue and combining with a rapid 3D imaging using light-sheet fluorescence microscopy. As a result, we developed versatile immunohistochemical method and a series of chemical probes for vasculature, cytoplasm, and senile plaques in human brain tissue.

Academic Significance and Societal Importance of the Research Achievements

本研究は透明化処理に適用可能な蛍光プローブを探索・設計するための一般的な化学的概念の創出を目的としており、先駆的な研究課題である。これにより、有機化学者がヒト脳剖検サンプルを用いた蛍光プローブ開発を展開するための基盤を確立できるため、化学と医学の間の壁を突破するケミカルメディシンを拓く一つのマイルストーンになりえる。また、3次元神経病理学が確立されることにより、「定量的な診断基準の確立」・「病変部位の網羅的探索」・「立体構造の異常に基づく疾患概念の体系化」が期待され、神経病理学分野の発展に大きく寄与できる。

Report

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

    (29 results)

All 2022 2021 2020 2019 2018

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (18 results) (of which Int'l Joint Research: 4 results,  Invited: 13 results) Book (2 results)

  • [Journal Article] Spatiotemporal dynamics of clonal selection and diversification in normal endometrial epithelium2022

    • Author(s)
      Yamaguchi Manako、Nakaoka Hirofumi、Suda Kazuaki、Yoshihara Kosuke、Ishiguro Tatsuya、Yachida Nozomi、Saito Kyota、Ueda Haruka、Sugino Kentaro、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Revathidevi Sundaramoorthy、Motoyama Teiichi、Tainaka Kazuki、Verhaak Roel G. W.、Inoue Ituro、Enomoto Takayuki
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 943-943

    • DOI

      10.1038/s41467-022-28568-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanical load regulates bone growth via periosteal Osteocrin2021

    • Author(s)
      Watanabe-Takano H., Ochi H., Chiba A., Matsuo A., Kanai Y., Fukuhara S., Ito N., Sako K., Miyazaki T., Tainaka K., Harada I., Sato S., Sawada Y., Minamino N., Takeda S., Ueda H.R., Yasoda A., Mochizuki N.
    • Journal Title

      Cell Reports

      Volume: 36 Issue: 2 Pages: 109380-109380

    • DOI

      10.1016/j.celrep.2021.109380

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Using a new three-dimensional CUBIC tissue-clearing method to examine the brain during experimental cerebral malaria.2021

    • Author(s)
      Matsuo-Dapaah J, Lee MSJ, Ishii KJ, Tainaka K, Coban C.
    • Journal Title

      Int Immunol.

      Volume: 33 Issue: 11 Pages: 587-594

    • DOI

      10.1093/intimm/dxab060

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-organ analysis of TGF-β-mediated remodelling of the tumour microenvironment by tissue clearing.2021

    • Author(s)
      Kubota SI, Takahashi K, Mano T, Matsumoto K, Katsumata T, Shi S, Tainaka K, Ueda HR, Ehata S, Miyazono K.
    • Journal Title

      Commun. Biol.

      Volume: 4 Issue: 1 Pages: 294-294

    • DOI

      10.1038/s42003-021-01786-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional understanding of the morphological complexity of the human uterine endometrium2021

    • Author(s)
      Yamaguchi Manako、Yoshihara Kosuke、Suda Kazuaki、Nakaoka Hirofumi、Yachida Nozomi、Ueda Haruka、Sugino Kentaro、Mori Yutaro、Yamawaki Kaoru、Tamura Ryo、Ishiguro Tatsuya、Motoyama Teiichi、Watanabe Yu、Okuda Shujiro、Tainaka Kazuki、Enomoto Takayuki
    • Journal Title

      iScience

      Volume: 24 Issue: 4 Pages: 102258-102258

    • DOI

      10.1016/j.isci.2021.102258

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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] Neurotransmission through dopamine D1 receptors is required for aversive memory formation and Arc activation in the cerebral cortex2020

    • Author(s)
      Saito Nae、Tainaka Kazuki、Macpherson Tom、Hikida Takatoshi、Yamaguchi Shun、Sasaoka Toshikuni
    • Journal Title

      Neuroscience Research

      Volume: - Pages: 58-65

    • DOI

      10.1016/j.neures.2020.04.006

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation.2019

    • Author(s)
      Inoue M, Saito R, Kakita A, Tainaka K.
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 29 Issue: 15 Pages: 1886-1890

    • DOI

      10.1016/j.bmcl.2019.05.049

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents.2018

    • Author(s)
      Tainaka K, Murakami TC, Susaki EA, Shimizu C, Saito R, Takahashi K, Hayashi-Takagi A, Sekiya H, Arima Y, Nojima S, Ikemura M, Ushiku T, Shimizu Y, Murakami M, Tanaka KF, Iino M, Kasai H, Sasaoka T, Kobayashi K, Miyazono K, Morii E, Isa T, Fukayama M, Kakita A, Ueda HR.
    • Journal Title

      Cell Rep.

      Volume: 24 Issue: 8 Pages: 2196-2210

    • DOI

      10.1016/j.celrep.2018.07.056

    • NAID

      120006542018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 組織透明化の化学的アプローチ2021

    • Author(s)
      田井中一貴
    • Organizer
      ISNAC2021_若手フォーラム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 生体組織透明化技術CUBICによる包括的3Dイメージング技術2021

    • Author(s)
      田井中一貴
    • Organizer
      第757回 新潟医学会例会シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 組織透明化・3Dイメージング技術による3次元神経病理学2021

    • Author(s)
      田井中一貴
    • Organizer
      2021年度 生理研研究会 機能的神経回路の構築と動作を支える分子細胞基盤
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ヒト脳組織透明化・3Dイメージングによる3次元神経病理学2021

    • Author(s)
      田井中一貴
    • Organizer
      第127回日本解剖学会総会・企画シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脳透明化2020

    • Author(s)
      田井中一貴
    • Organizer
      第3回若手育成セミナー「神経回路の可視化・操作・モデリングのための最先端技術」
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] CUBIC: Whole-brain/body imaging with single-cell resolution using hydrophilic chemical cocktails2019

    • Author(s)
      Kazuki Tainaka
    • Organizer
      International Symposium of Biofunctional Chemistry
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CUBIC:生体組織透明化による包括的3Dイメージング技術2019

    • Author(s)
      田井中一貴
    • Organizer
      新潟医学会特別講演
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] CUBIC: 組織透明化技術による3Dイメージング2019

    • Author(s)
      田井中一貴
    • Organizer
      第60回新潟生化学懇話会プログラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 3D 神経病理学に向けたホールマウント染色手法の開発2019

    • Author(s)
      田井中 一貴・齋藤 理恵・井上 雅文・柿田 明美
    • Organizer
      第60回日本神経病理学会総会学術研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Comprehensive 3D Imaging by Tissue Clearing Technique CUBIC2019

    • Author(s)
      Kazuki Tainaka
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織透明化による3D神経病理学2019

    • Author(s)
      田井中一貴
    • Organizer
      第16回 日本病理学会カンファレンス
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] CUBIC: Whole-organ, whole-body imaging with single-cell resolution using chemical cocktails2019

    • Author(s)
      Kazuki Tainaka
    • Organizer
      リエゾンラボ炎症シンポジウムin北海道大学
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 有機化学が拓く次世代3D組織化学2019

    • Author(s)
      田井中一貴
    • Organizer
      第5回 北海道大学部局横断シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] CUBIC: Whole-brain/body imaging with single-cell resolution using hydrophilic chemical cocktails2019

    • Author(s)
      Kazuki Tainaka
    • Organizer
      BRI The 9th international symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 組織透明化技術CUBICによる3D神経病理学2018

    • Author(s)
      田井中一貴
    • Organizer
      日本ケミカルバイオロジー学会 第13回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 組織透明化技術CUBICによる3D神経病理学2018

    • Author(s)
      田井中一貴
    • Organizer
      第107回日本病理学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 水溶性試薬による組織透明化の化学2018

    • Author(s)
      田井中一貴
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of 3D neuropathology based on tissue clearing technique2018

    • Author(s)
      Kazuki Tainaka, Rie Saito, Akiyoshi Kakita
    • Organizer
      ICN2018, 19th International Congress of Neuropathology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Book] 『病理と臨床』2020年3月号 組織・細胞の透明化2020

    • Author(s)
      田井中一貴
    • Total Pages
      4
    • Publisher
      文光堂
    • Related Report
      2019 Annual Research Report
  • [Book] 『ぶんせき』2019年10号 入門講座 組織透明化技術と蛍光顕微鏡 3D イメージング2019

    • Author(s)
      田井中一貴
    • Total Pages
      8
    • Publisher
      公益社団法人 日本分析化学会
    • Related Report
      2019 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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