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Cellular diversity and hierarchy of colorectal cancer

Research Project

Project/Area Number 16K14620
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

Yao Ryoji  公益財団法人がん研究会, がん研究所 細胞生物部, 部長 (80291095)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸がん / オルガノイド / 1細胞解析 / 大腸がんオルガノイド / 一細胞解析 / 癌
Outline of Final Research Achievements

Cellular diversity of cancer tissue contributes to several biological aspects of cancer including resistance to chemotherapy. We have established patient-derived organoid from advanced colorectal cancer and have explored the cellular diversity. Single cell expression analysis (scRNA-seq) successfully identified five clusters determined by the distinct differentiation and proliferation markers. We have performed further detailed DE analysis, and have successfully identified the stem cell marker. The stem cells were visualized by genome editing of the organoid, and shown to have self-renew and multiple differentiation potentials. The ablation assay demonstrated that the stem cells were requited for efficient maintenance and growth of the organoids. These observations demonstrated the cellular diversity and hierarchy of cancer tissue and may provide the cue to develop efficient therapeutics.

Academic Significance and Societal Importance of the Research Achievements

1細胞発現解析(scRNA-seq)により、進行大腸がん手術検体由来の三次元培養オルガノイドが、複数の細胞クラスターで構成されることが明らかになったことにより、がん組織の理解、さらにこれまで不可能であったヒトがん組織の解析が可能になった点で、高い学術的意義を有する。さらに、今後のがん治療法開発の理論的な根拠を与えることに加えて、オルガノイドが薬剤開発の研究リソースとして貢献できることを意味しており、社会的意義は大きい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] IFN/STAT signaling controls tumorigenesis and the drug response in colorectal cancer2019

    • Author(s)
      Sakahara Mizuho、Okamoto Takuya、Oyanagi Jun、Takano Hiroshi、Natsume Yasuko、Yamanaka Hitomi、Kusama Daisuke、Fusejima Mishio、Tanaka Norio、Mori Seiich、Kawachi Hiroshi、Ueno Masashi、Sakai Yoshiharu、Noda Tetsuo、Nagayama Satoshi、Yao Ryoji
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 4 Pages: 1293-1305

    • DOI

      10.1111/cas.13964

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved phosphoproteomic analysis for phosphosignaling and active-kinome profiling in Matrigel-embedded spheroids and patient-derived organoids2018

    • Author(s)
      Abe Yuichi、Tada Asa、Isoyama Junko、Nagayama Satoshi、Yao Ryoji、Adachi Jun、Tomonaga Takeshi
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 11401-11401

    • DOI

      10.1038/s41598-018-29837-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling2018

    • Author(s)
      Kawasaki Natsumi、Isogaya Kazunobu、Dan Shingo、Yamori Takao、Takano Hiroshi、Yao Ryoji、Morishita Yasuyuki、Taguchi Luna、Morikawa Masato、Heldin Carl-Henrik、Noda Tetsuo、Ehata Shogo、Miyazono Kohei、Koinuma Daizo
    • Journal Title

      Cell Discovery

      Volume: 4 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41421-017-0001-2

    • NAID

      120006902800

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.2016

    • Author(s)
      1.Yao, R., Oyanagi, J. Natsume, Y. Kusama, D., Kato, Y., Nagayama, S. & Noda, T.
    • Journal Title

      Oncogene

      Volume: Epub ahead of print Issue: 47 Pages: 1-11

    • DOI

      10.1038/onc.2016.148

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 大腸がん組織を構成する細胞集団の多様性と階層性2019

    • Author(s)
      八尾 良司
    • Organizer
      第1回鹿児島がんと代謝セミナー
    • Related Report
      2018 Annual Research Report
  • [Presentation] IFN/STAT signaling controls tumorigenesis of colorectal cancers2019

    • Author(s)
      八尾 良司
    • Organizer
      11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2018 Annual Research Report
  • [Presentation] Mouse model of metastatic colorectal cancer by orthotopic transplantation of patient derived organoids2019

    • Author(s)
      岡本 拓也
    • Organizer
      AACR Annual Meeting 2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] 体細胞変異と遺伝的背景による大腸がん薬剤感受性制御機構2018

    • Author(s)
      八尾 良司
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 患者由来大腸がんオルガノイドを用いた転移モデルマウス2018

    • Author(s)
      岡本 拓也
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 遺伝的背景による大腸がんの発生・薬剤感受性制御機構2018

    • Author(s)
      八尾 良司
    • Organizer
      第1回 細胞社会ダイバーシティーの統合的解析
    • Related Report
      2017 Research-status Report
  • [Presentation] 遺伝子改変マウスを用いた腫瘍発生機構の解析2018

    • Author(s)
      坂原 瑞穂
    • Organizer
      新学術領域「細胞ダイバース」第1回若手ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] 大腸がんオルガノイドを用いた腫瘍発生機構の解析2018

    • Author(s)
      岡本 拓也
    • Organizer
      新学術領域「細胞ダイバース」第1回若手ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] 家族性大腸腺腫症オルガノイドを用いた発がん機構解明2017

    • Author(s)
      八尾 良司、小柳 潤、長山 聡、野田 哲生
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] TUFT1-RABAP1を介した小胞輸送制御によるmTORC1シグナルの新規活性化機構の解析2017

    • Author(s)
      川崎 夏実、磯谷 一暢、旦 慎吾、矢守 隆夫、高野 洋志、八尾 良司、田口 瑠奈、森川 真大、野田 哲生、江幡 正悟、宮園 浩平、鯉沼 代造
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 同一症例からの原発巣および転移巣由来のオルガノイドを利用した機能解析2017

    • Author(s)
      長山 聡、八尾 良司
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝臓オルガノイドを用いた肥満誘導性肝臓がん発症モデルの構築及び、がんの起源細胞の解明2017

    • Author(s)
      窪田 達寛、安藤 達也、福井 優也、渡辺 喜洋、小澤 崇之、蒲池 史卓、八尾 良司、佐藤 俊朗、大谷 直子
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Research-status Report
  • [Presentation] TUFT1は核周囲への小胞の集積を促進しmTORC1を活性化する2016

    • Author(s)
      川崎夏美、磯谷一暢、旦慎吾、矢守隆夫、高野洋志、八尾良司、田口瑠奈、森川真大、野田哲生、江幡正悟、宮園浩平、鯉沼代造
    • Organizer
      第75回日本癌学会
    • Place of Presentation
      横浜市(神奈川県)
    • Year and Date
      2016-10-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 消化管幹細胞の紡錘体を標的とした消化管腫瘍の抑制2016

    • Author(s)
      八尾良司、小柳潤、長山聡、野田哲生
    • Organizer
      第75回日本癌学会
    • Place of Presentation
      横浜市(神奈川県)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] eveloping the novel cancer therapeutics targeting a mitotic protein, TACC32016

    • Author(s)
      Ryoji Yao
    • Organizer
      RIKEN-MAX Plank Joint Research Center for Systems Chemical Biology, The 5th symposium
    • Place of Presentation
      ベルリン(ドイツ)
    • Year and Date
      2016-04-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] マウス表現型解析スタンダード2016

    • Author(s)
      1. 美野輪治、八尾良司
    • Total Pages
      347
    • Publisher
      羊土社
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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