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Cell lineage analysis of changes in characteristics of pancreatic cancer cells at single cell level(Fostering Joint International Research)

Research Project

Project/Area Number 15KK0314
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionYokohama City University

Principal Investigator

Sekine Keisuke  横浜市立大学, 医学部, 講師 (00323569)

Research Collaborator CAMP J. Gray  Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Group leader
TREUTLEIN Barbara  Max Planck Institute for Evolutionary Anthropology, Max Planck Research Group on Single Cell Genomics, Group leader and Assistant Professor at TU Munich
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥11,000,000、Indirect Cost: ¥3,300,000)
Keywordsオルガノイド / 膵癌 / iPSC / Organoid / シングルセルゲノミクス / 癌幹細胞 / 癌微小環境 / シングルセル / RNAシークエンス
Outline of Final Research Achievements

In this study, single-cell RNA sequencing of human three-dimensional organs was carried out with Dr. Camp and Dr. Treutlein others under at Max Planck Institute, Germany.
We identified molecules whose expression could only be seen when multiple cell types were mixed together to generate organoid. By analyzing in detail, we identified signal candidates involved in cell-cell interactions. We performed functional analysis based on the information of this signal candidate molecule and revealed that multiple signal candidates actually contribute to steric intercellular interaction (Camp JG, Sekine K et al, Nature 2017).

Academic Significance and Societal Importance of the Research Achievements

本研究によって、生体内で見られる複数の細胞種により構成される立体的な組織における細胞間相互作用の一旦を明らかにし、従来の平面培養における課題を明らかにした。また、本手法によって立体的な細胞間相互作用の新たな解析手法を提示することが出来た。これらの成果は、幹細胞生物学を背景に立体臓器の再構成技術をもつ日本側研究者とシングルセルRNAシークエンス解析の先駆者であるドイツ側研究者の国際共同研究によってはじめて成しえた成果と言える。

Report

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

    (32 results)

All 2019 2018 2017 2016

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (16 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Book (1 results) Patent(Industrial Property Rights) (4 results)

  • [Int'l Joint Research] シンシナティ小児病院(米国)2018

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] マックスプランク進化人類学研究所(ドイツ)2017

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Self-Condensation Culture Enables Vascularization of Tissue Fragments for Efficient Therapeutic2018

    • Author(s)
      Yoshinobu Takahashi, Keisuke Sekine, Tatsuya Kin, Takanori Takebe, Hideki Taniguchi
    • Journal Title

      Cell Reports

      Volume: 6 Issue: 6 Pages: 1620-1629

    • DOI

      10.1016/j.celrep.2018.03.123

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Optimal Hypoxia Regulates Human iPSC-Derived Liver Bud Differentiation through Intercellular TGFB Signaling2018

    • Author(s)
      Ayabe Hiroaki、Anada Takahisa、Kamoya Takuo、Sato Tomoya、Kimura Masaki、Yoshizawa Emi、Kikuchi Shunyuu、Ueno Yasuharu、Sekine Keisuke、Camp J. Gray、Treutlein Barbara、Ferguson Autumn、Suzuki Osamu、Takebe Takanori、Taniguchi Hideki
    • Journal Title

      Stem Cell Reports

      Volume: 11 Issue: 2 Pages: 306-316

    • DOI

      10.1016/j.stemcr.2018.06.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recapitulation of hepatitis B virus?host interactions in liver organoids from human induced pluripotent stem cells2018

    • Author(s)
      Nie Yun-Zhong、Zheng Yun-Wen、Miyakawa Kei、Murata Soichiro、Zhang Ran-Ran、Sekine Keisuke、Ueno Yasuharu、Takebe Takanori、Wakita Takaji、Ryo Akihide、Taniguchi Hideki
    • Journal Title

      EBioMedicine

      Volume: 35 Pages: 114-123

    • DOI

      10.1016/j.ebiom.2018.08.014

    • NAID

      120007128498

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human iPSC-Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids.2018

    • Author(s)
      Zhang R-R, Koido M, Tadokoro T, Ouchi R, Matsuno T, Ueno Y, Sekine K, Takebe T*, Taniguch H
    • Journal Title

      Stem Cell Reports

      Volume: 10 Issue: 3 Pages: 780-793

    • DOI

      10.1016/j.stemcr.2018.01.006

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multilineage communication regulates human liver bud self-organization from pluripotency.2017

    • Author(s)
      Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S, Kageyama J, Damm G, Seehofer D, Belicova L, Bickle M, Barsacchi R, Okuda R, Yoshizawa E, Kimura M, Ayabe H, Taniguchi H, Takebe T*, Treutlein B
    • Journal Title

      Nature

      Volume: 546 Issue: 7659 Pages: 533-534

    • DOI

      10.1038/nature22796

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells.2017

    • Author(s)
      Takebe T*, Sekine K, Kimura M, Yoshizawa E, Funayama S, Nakanishi N, Hisai T, Kobayashi T, Mori A, Ayano S, Ejiri Y, Amimoto N, Yamazaki Y, Ogawa S, Ishikawa M, Kiyota Y, Ueno Y, Taniguchi H
    • Journal Title

      Cell Reports

      Volume: 21 Issue: 10 Pages: 2661-2670

    • DOI

      10.1016/j.celrep.2017.11.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells2017

    • Author(s)
      Chang Po-Hsiang、Sekine Keisuke、Chao Hsiao-Mei、Hsu Shan-hui、Chern Edward
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 45751-45751

    • DOI

      10.1038/srep45751

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Liver Regeneration Using Cultured Liver Bud2017

    • Author(s)
      Sekine K, Takebe T, Taniguchi H.
    • Journal Title

      Methods Mol Biol

      Volume: 1597 Pages: 207-216

    • DOI

      10.1007/978-1-4939-6949-4_15

    • ISBN
      9781493969470, 9781493969494
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nutritional modulation of mouse and human liver bud growth through a branched-chain amino acid metabolism.2017

    • Author(s)
      Koike H, Zhang RR, Ueno Y, Sekine K, Zheng YW, Takebe T, Taniguchi H.
    • Journal Title

      Development

      Volume: 144(6) Pages: 1018-1024

    • DOI

      10.1242/dev.143032

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Generation of three-dimensional cancer tissue using patient-derived pancreatic cancer cells2019

    • Author(s)
      Keisuke Sekine
    • Organizer
      Asia-Pacific Scientific Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 再生医療応用へ向けたiPSC肝芽製造技術の開発2018

    • Author(s)
      関根圭輔
    • Organizer
      幹細胞の培養法・培養工学のためのコンソーシアム 第三回シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒト組織三次元的再構成技術を用いたヒューマンバイオロジーの解析2018

    • Author(s)
      関根圭輔
    • Organizer
      第11回Symphony
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 患者由来膵癌細胞を用いた三次元的癌組織の人為的創出2018

    • Author(s)
      関根圭輔
    • Organizer
      講演会:新しい治療法の開発を目指す患者由来がんモデル
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトiPSC肝芽の臨床応用に向けた安全性評価手法の確立2018

    • Author(s)
      濱田 侑希、関根 圭輔、都築 周作、小林 達也、上野 康晴、武部 貴則、谷口 英樹
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 血管化膵島移植による革新的糖尿病治療法の確立2017

    • Author(s)
      高橋禎暢、武部貴則、小池直人、関根圭輔、谷口英樹
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 癌微小環境を模倣した患者由来ヒト膵がんオルガノイドの創出2017

    • Author(s)
      奥田 諒、関根 圭輔、上野康晴 康晴、佐藤 準也、高橋 正希、井上 達也、金子 千夏、碓井 彩華、谷口 英樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドは薬剤耐性を示す2017

    • Author(s)
      関根 圭輔、奥田 諒、井上 達也、金子 千夏、碓井 彩華、上野 康晴、谷口 英樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腫瘍微小環境を伴う膵癌オルガノイドは薬剤耐性を示す2017

    • Author(s)
      碓井 彩華、奥田 諒、関根 圭輔、上野 康晴、佐藤 準也、高橋 正希、井上 達也、金子 千夏、谷口 英樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 腫瘍微小環境を伴う膵癌オルガノイドはin vitroで治療抵抗性を示す2017

    • Author(s)
      金子 千夏、奥田 諒、関根 圭輔、上野 康晴、佐藤 準也、高橋 正希、井上 達也、碓井 彩華、谷口 英樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 微小環境を伴うヒト膵オルガノイドの再構成に基づく新規膵癌薬剤評価系の構築2017

    • Author(s)
      上野 康晴、奥田 諒、金子 千夏、碓井 彩華、関根 圭輔、谷口 英樹
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] シングルセルレベルでのiPSC肝芽構成細胞のポピュレーションヘテロジェネイティ解析2016

    • Author(s)
      関根 圭輔、J. Gray Camp、Barbara Treutlein、武部 貴則、谷口 英樹
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドの創出2016

    • Author(s)
      奥田諒、関根圭輔、上野康晴、佐藤準也、高橋正希、濱中香織、谷口英樹
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 臓器形成におけるヘテロジェネイティの理解と制御2016

    • Author(s)
      武部 貴則、関根 圭輔、谷口 英樹
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 腫瘍微小環境を模倣するヒト膵癌オルガノイドの創出2016

    • Author(s)
      奥田 諒、高橋 正希、佐藤 準也、関根 圭輔、上野 康晴、谷口 英樹
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] De novo generation of organ buds from stem cells2016

    • Author(s)
      Keisuke Sekine
    • Organizer
      21st NAT Congress
    • Place of Presentation
      Nantes, France
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Book] Organ Regeneration Based on Developmental Biology2017

    • Author(s)
      Keisuke Sekine, Takanori Takebe, Hideki Taniguchi
    • Total Pages
      257
    • Publisher
      Springer book
    • ISBN
      9789811037689
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 未分化細胞の分化抵抗性評価法2019

    • Inventor(s)
      関根圭輔、谷口英樹
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-005892
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 未分化細胞検出法2018

    • Inventor(s)
      関根圭輔、谷口英樹
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-115025
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 上皮間葉転換関連分子を用いた癌評価法2018

    • Inventor(s)
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-080581
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 再構成癌組織を用いた薬剤評価方法2018

    • Inventor(s)
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Holder
      関根圭輔、谷口英樹、上野康晴、奥田諒、森永聡一郎、宮城洋平
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-080585
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-10-04   Modified: 2020-03-30  

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