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Development of novel toxicity evaluation system based on whole-body/organ imaging technique with single cell resolution

Research Project

Project/Area Number 16K15124
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pharmacology in pharmacy
Research InstitutionNiigata University

Principal Investigator

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

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords組織透明化 / 全身イメージング / 毒性評価システム / 3Dイメージング / 透明化プロトコール / 骨組織の透明化 / がん細胞の検出 / 生体組織透明化
Outline of Final Research Achievements

Current pathology relies on cell-based pathology. Therefore, in order to develop more sensitive and comprehensive toxicity test, it is important to visualize individual cell and detect cellular degeneration in entire body. In this study, we aimed at developing a novel toxicity evaluation system based on whole-body/organ imaging technique with single cell resolution. To this end, we developed further improved whole-body clearing protocol by comprehensive chemical screening for a series of clearing factors. The new CUBIC protocol enables whole-body and whole-organ imaging of cancer metastasis of adult mice at single-cell resolution. The expanded highly-cleared brain enabled us to construct a mouse brain atlas with single-cell annotation. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto our atlas revealed the existence of distinct functional structures.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (18 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing2018

    • Author(s)
      Murakami Tatsuya C.、Mano Tomoyuki、Saikawa Shu、Horiguchi Shuhei A.、Shigeta Daichi、Baba Kousuke、Sekiya Hiroshi、Shimizu Yoshihiro、Tanaka Kenji F.、Kiyonari Hiroshi、Iino Masamitsu、Mochizuki Hideki、Tainaka Kazuki、Ueda Hiroki R.
    • Journal Title

      Nat Neurosci

      Volume: 21 Issue: 4 Pages: 627-637

    • DOI

      10.1038/s41593-018-0109-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock2017

    • Author(s)
      Shinohara Yuta、Koyama Yohei M.、Ukai-Tadenuma Maki、Hirokawa Takatsugu、Kikuchi Masaki、Yamada Rikuhiro G.、Ukai Hideki、Fujishima Hiroshi、Umehara Takashi、Tainaka Kazuki、Ueda Hiroki R.
    • Journal Title

      Molecular Cell

      Volume: 67 Issue: 5 Pages: 783-798

    • DOI

      10.1016/j.molcel.2017.08.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution2017

    • Author(s)
      Kubota Shimpei I.、Takahashi Kei、Nishida Jun、Morishita Yasuyuki、Ehata Shogo、Tainaka Kazuki、Miyazono Kohei、Ueda Hiroki R.
    • Journal Title

      Cell Reports

      Volume: 20 Issue: 1 Pages: 236-250

    • DOI

      10.1016/j.celrep.2017.06.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical Principles in Tissue Clearing and Staining Protocols for Whole-Body Cell Profiling.2016

    • Author(s)
      Tainaka K, Kuno A, Kubota SI, Murakami T, Ueda HR.
    • Journal Title

      Annu. Rev. Cell Dev. Biol.

      Volume: 32 Issue: 1 Pages: 713-741

    • DOI

      10.1146/annurev-cellbio-111315-125001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 組織透明化技術と包括的3Dイメージング2018

    • Author(s)
      田井中一貴
    • Organizer
      イメージング技術の融合による医学・生命科学の新たな地平の開拓
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] タンパク質の老化基盤解析に向けたヒト脳組織透明化技術の確立2018

    • Author(s)
      田井中一貴
    • Organizer
      新学術領域第7回班会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体組織透明化技術CUBICによる3次元神経病理学の開発2018

    • Author(s)
      田井中一貴
    • Organizer
      第7回 新潟脳研-霊長研-生理研合同シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 透明化技術を用いた包括的3Dイメージング技術2018

    • Author(s)
      田井中一貴
    • Organizer
      第一回リエゾンラボユニット間シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体組織透明化技術CUBICによる3D神経病理学の開発2017

    • Author(s)
      田井中一貴
    • Organizer
      第58回日本神経病理学会総会学術研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CUBIC: Whole-organ, whole-body imaging at single-cell resolution using aminoalcohol-based chemical cocktails2017

    • Author(s)
      田井中一貴
    • Organizer
      第58回日本神経病理学会総会学術研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 3D免疫染色によるタンパク質の老化基盤の解析2017

    • Author(s)
      田井中一貴
    • Organizer
      新学術領域第6回班会議
    • Related Report
      2017 Annual Research Report
  • [Presentation] 生体組織透明化による包括的3次元イメージング技術CUBIC2017

    • Author(s)
      田井中一貴
    • Organizer
      日本ケミカルバイオロジー学会 第12回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CUBIC:生体組織透明化による包括的3Dイメージング技術2017

    • Author(s)
      田井中一貴
    • Organizer
      北海道大学遺伝子病制御研究所セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 組織透明化技術と脳コネクトーム2017

    • Author(s)
      田井中一貴
    • Organizer
      第47回新潟神経学夏期セミナー
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 生体組織透明化技術CUBIC2017

    • Author(s)
      田井中一貴
    • Organizer
      第15回 新潟内耳疾患研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] CUBIC: Whole-organ, whole-body imaging with single-cell resolution using chemical cocktails2017

    • Author(s)
      田井中一貴
    • Organizer
      Brain Protein Aging and Dementia Control 2nd International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体組織透明化による全身丸ごとイメージング技術CUBIC2016

    • Author(s)
      田井中一貴
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザかるぽーと(高知県高知市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 光透過性に優れた生物材料を調整するための組成物およびその利用2016

    • Inventor(s)
      上田泰己、田井中一貴、村上達哉
    • Industrial Property Rights Holder
      上田泰己、田井中一貴、村上達哉
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-092025
    • Filing Date
      2016-04-28
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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