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cellular diversity in mammalian intestinela tissue

Planned Research

Project AreaIntegrated analysis and regulation of cellular diversity
Project/Area Number 17H06333
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 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) 2017-06-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥104,650,000 (Direct Cost: ¥80,500,000、Indirect Cost: ¥24,150,000)
Fiscal Year 2021: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2020: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2019: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2018: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2017: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Keywords消化管組織 / がんモデルマウス / オルガノイド / 3次元培養オルガノイド / 遺伝子改変マウス / ゲノム編集 / 遺伝子変異マウス / 3次元培養オルガノイド / 三次元培養オルガノイド
Outline of Final Research Achievements

To elucidate the cellular diversity in intestinal tissue and their alteration induced by driver mutations found in human colorectal cancers, we established a series of conditional knockout mice and their organoids. Single cell expression analysis of organoids followed by informatics analyses suggested the cellular diversity in norma intestine and their alterations by the driver mutations. Notably, they alters not only cellular diversity in intestinal epithelial cells, but also affects stromal cells in their microenvironment. These alterations were histologically validated in mouse models. Overall, this study revealed the cellular heterogeniety of intestinal tissues in normal and mutant tissues,, and provide the clue to develop the treatment of intestinal tumor by targeting interaction between intestinal epithelia cells and microenvironment.

Academic Significance and Societal Importance of the Research Achievements

本研究開発では、哺乳動物の消化管組織の細胞多様性とがん化に伴う変化を明らかにした。その結果、ヒト大腸がんの発生に関与する遺伝子変異は、がん組織を変化させるのみでなく、周囲の微小環境にいる間質細胞にも影響することが明らかになった。これらの結果から、現在有効な分子標的薬がない、RAS変異陽性大腸がんに対して、がん組織と微小環境との相互作用を標的とする治療戦略を提唱することができた。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (44 results)

All 2021 2020 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (34 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] A protocol for efficient CRISPR-Cas9-mediated knock-in in colorectal cancer patient-derived organoids2021

    • Author(s)
      Okamoto Takuya、Natsume Yasuko、Yamanaka Hitomi、Fukuda Mayuko、Yao Ryoji
    • Journal Title

      STAR Protocols

      Volume: 2 Issue: 4 Pages: 100780-100780

    • DOI

      10.1016/j.xpro.2021.100780

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Probing the tumorigenic potential of genetic interactions reconstituted in murine fallopian tube organoids2021

    • Author(s)
      Maru Yoshiaki、Tanaka Naotake、Tatsumi Yasutoshi、Nakamura Yuki、Yao Ryoji、Noda Tetsuo、Itami Makiko、Hippo Yoshitaka
    • Journal Title

      The Journal of Pathology

      Volume: 255 Issue: 2 Pages: 177-189

    • DOI

      10.1002/path.5752

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Analysis of Patient-Matched PDOs Revealed a Reduction in OLFM4-Associated Clusters in Metastatic Lesions in Colorectal Cancer2021

    • Author(s)
      Okamoto Takuya、duVerle David、Yaginuma Katsuyuki、Natsume Yasuko、Yamanaka Hitomi、Kusama Daisuke、Fukuda Mayuko、Yamamoto Mayuko、Perraudeau Fanny、Srivastava Upasna、Kashima Yukie、Suzuki Ayako、Kuze Yuuta、Takahashi Yu、Ueno Masashi、Sakai Yoshiharu、Noda Tetsuo、Tsuda Koji、Suzuki Yutaka,Nagayama Satoshi,Yao Ryoji
    • Journal Title

      Stem Cell Reports

      Volume: 16 Issue: 4 Pages: 954-967

    • DOI

      10.1016/j.stemcr.2021.02.012

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the RAS signaling network in response to MEK inhibition using organoids derived from a familial adenomatous polyposis patient2020

    • Author(s)
      Osumi Hiroki、Muroi Atsushi、Sakahara Mizuho、Kawachi Hiroshi、Okamoto Takuya、Natsume Yasuko、Yamanaka Hitomi、Takano Hiroshi、Kusama Daisuke、Shinozaki Eiji、Ooki Akira、Yamaguchi Kensei、Ueno Masashi、Takeuchi Kengo、Noda Tetsuo、Nagayama Satoshi、Koshikawa Naohiko、Yao Ryoji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17455-17455

    • DOI

      10.1038/s41598-020-74530-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MCRIP1 promotes the expression of lung-surfactant proteins in mice by disrupting CtBP-mediated epigenetic gene silencing2019

    • Author(s)
      Weng Jane S.、Nakamura Takanori、Moriizumi Hisashi、Takano Hiroshi、Yao Ryoji、Takekawa Mutsuhiro
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 227-227

    • DOI

      10.1038/s42003-019-0478-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice2019

    • Author(s)
      Ito C, Akutsu H, Yao R, Yoshida K, Yamatoya K, Mutoh T, Makino T, Aoyama K, Ishikawa H, Kunimoto K, Tsukita S, Noda T, Kikkawa M, Toshimori K.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 14249-14249

    • DOI

      10.1038/s41598-019-50516-2

    • URL

      https://pure.teikyo.jp/en/publications/8a402310-6282-4f36-be37-3937739f940e

    • Related Report
      2019 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

    • URL

      https://pure.teikyo.jp/en/publications/1ee5929f-9e7c-4d39-ad9e-8f2d6947ed29

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 転移・再発に伴う大腸がん組織の細胞不均一性の変化2021

    • Author(s)
      八尾 良司
    • Organizer
      第25回日本がん分子標的治療学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Kras変異に伴う消化管腫瘍組織の変化2021

    • Author(s)
      坂原 瑞穂、八尾 良司
    • Organizer
      2021年度先端モデル動物支援プラットフォーム「若手支援技術講習会」
    • Related Report
      2021 Annual Research Report
  • [Presentation] Patient derived organoidsの基本と応用2021

    • Author(s)
      八尾 良司
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 転移に伴う細胞不均一性の変化2021

    • Author(s)
      八尾 良司、長山 聡、岡本 拓也
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒト大腸がん由来オルガノイド移植マウスモデルにおける転移播種がん細胞のEMT解析2021

    • Author(s)
      柳沼 克幸、岡本 拓也、長山 聡、八尾 良司
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来大腸がんオルガノイド同所移植マウスモデルにおける転移播種細胞2021

    • Author(s)
      岡本 拓也、柳沼 克幸、長山 聡、小濱 和貴、八尾 良司
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来大腸癌オルガノイドを用いた細胞分化プロセスの解析2021

    • Author(s)
      長山 聡、岡本 拓也、八尾 良司
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 患者由来オルガノイドを用いた大腸がん組織の細胞不均一性の解明2021

    • Author(s)
      八尾 良司
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん患者由来オルガノイドを用いた研究2020

    • Author(s)
      八尾 良司
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト大腸がんオルガノイド同所移植マウスモデルにおける転移腫瘍の発生とEMTマーカーの発現2020

    • Author(s)
      柳沼 克幸、岡本 拓也、長山 聡、八尾 良司
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 患者由来大腸がんオルガノイド同所移植マウスモデルにおける転移播種細胞の同定2020

    • Author(s)
      岡本 拓也、柳沼 克幸、長山 聡、八尾 良司
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 大腸癌組織を構成する細胞集団の多様性2020

    • Author(s)
      長山 聡、岡本 拓也、八尾 良司
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 患者由来オルガノイドを用いた大腸がんの発生、転移・再発機構の解明2020

    • Author(s)
      八尾 良司
    • Organizer
      患者由来がんモデル講演会 -基礎研究から臨床応用まで-
    • Related Report
      2020 Annual Research Report
  • [Presentation] 消化管腫瘍発生における細胞多様性の役割2019

    • Author(s)
      坂原 瑞穂、八尾 良司
    • Organizer
      第4回公開シンポジウム「1細胞統合解析を駆使した組織内ダイバーシティー解明への挑戦」
    • Related Report
      2019 Annual Research Report
  • [Presentation] Comparative analysis of patient-derived organoids from primary colorectal cancer and matched metastatic and recurrent lesions.2019

    • Author(s)
      八尾 良司
    • Organizer
      Cell Symposium: Engineering Organoids and Organs
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 進行大腸がんオルガノイドの1細胞解析2019

    • Author(s)
      八尾 良司、長山 聡、鈴木 穰
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸がん同所移植モデルマウスを用いた転移の再現2019

    • Author(s)
      岡本 拓也、柳沼 克幸、長山 聡、八尾 良司
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸癌発生と薬剤感受性におけるIFN/STATシグナル伝達系の関与2019

    • Author(s)
      長山 聡、岡本 拓也、八尾 良司
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [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3回公開シンポジウム「1細胞統合解析を駆使した組織内ダイバーシティー解明への挑戦」
    • Related Report
      2018 Annual Research Report
  • [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] 大腸がんオルガノイドを用いた転移モデルマウス2019

    • Author(s)
      岡本 拓也
    • Organizer
      新学術領域「細胞ダイバース」第2回若手ワークショップ
    • Related Report
      2018 Annual Research Report
  • [Presentation] 消化管腫瘍発生におけるSTAT1の役割2019

    • Author(s)
      坂原 瑞穂
    • Organizer
      新学術領域「細胞ダイバース」第2回若手ワークショップ
    • 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明と制御
    • Related Report
      2017 Annual Research 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 Annual Research 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 Annual Research 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
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 発がん過程におけるストレス獲得耐性2017

    • Author(s)
      石川 冬木
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research 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
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research 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
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research 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
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Book] がん微小環境に1細胞レベルで挑む2021

    • Author(s)
      藤田 直也
    • Total Pages
      220
    • Publisher
      羊土社
    • ISBN
      9784758103961
    • Related Report
      2021 Annual Research Report

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Published: 2017-07-04   Modified: 2023-01-30  

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