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Molecular mechanism in the formation of the junction between different epithelia and in vitro recapitulation

Research Project

Project/Area Number 26253069
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKyoto University

Principal Investigator

Kawaguchi Yoshiya  京都大学, iPS細胞研究所, 教授 (60359792)

Co-Investigator(Kenkyū-buntansha) 山田 泰広  京都大学, iPS細胞研究所, 教授 (70313872)
Research Collaborator Sankoda Nao  
Project Period (FY) 2014-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥40,560,000 (Direct Cost: ¥31,200,000、Indirect Cost: ¥9,360,000)
Fiscal Year 2018: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2017: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2015: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2014: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywords食道胃接合部 / ES細胞 / 内胚葉上皮 / 組織形成 / オルガノイド / 内胚葉 / 食道 / 胃 / 前腸形成 / 臓器形成 / 食道・胃接合部 / 発生学 / 分化誘導
Outline of Final Research Achievements

In this study, we dissected the molecular mechanism in the formation of esophago-gastric (EC) junction during organogenesis. We found that Sox2 and Gata4 are initially co-expressed in the progenitor epithelia then expressions of Sox2 and Gata4 gradually formed gradients in inverse direction across the EC junction. Meanwhile, Fgf2 was induced in the gastric mesenchyme and proximal epithelial cells expressed FgfR2, resulting in the restricted activation of ERK at the junction. Separately sorted Gata4-low, -mid and -high epithelial cells at E13.5 formed stratified squamous, pseudostratified and simple columnar organoid, respectively, by in vitro culture. Furthermore, Fgf2 treatment to Gata4-low cells inhibited the differentiation to stratified squamous epithelia and stimulated the differentiation to transitional epithelia correspond to the E-C junction. Thus, spatio-temporal patterning of epithelial and mesenchymal Sox2/Gata4/ Fgf2 is important for the construction of EC junction.

Academic Significance and Societal Importance of the Research Achievements

食道―胃接合部や十二指腸Vater乳頭部、直腸歯状線、子宮頸部などの“異なる上皮の接点”は人体の複数の場所に存在し、腫瘍の発生母地になり得るという臨床上の共通した特性がある。
本研究では、これまで未解明であった発生期食道―胃接合部の形成機構/維持機構を明らかにした。まず、接合部形成位置を挟んでそれぞれの細胞運命を規定する転写因子が逆方向の濃度勾配を形成し、上皮―間質相互作用で一方の間質シグナルを誘導し、他方の上皮でその受容体を発現するという巧みな方法で、接合部に限局したシグナル活性化を来すことがわかった。他の“異なる上皮の接点”形成機構にも共通する可能性があり、今後の解明が待たれる。

Report

(6 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(25 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 17 results)

  • [Int'l Joint Research] Hebrew University(イスラエル)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Ptf1a inactivation in adult pancreatic acinar cells causes apoptosis through activation of the endoplasmic reticulum stress pathway2019

    • Author(s)
      Sakikubo Morito、Furuyama Kenichiro、Horiguchi Masashi、Hosokawa Shinichi、Aoyama Yoshiki、Tsuboi Kunihiko、Goto Toshihiko、Hirata Koji、Masui Toshihiko、Dor Yuval、Fujiyama Tomoyuki、Hoshino Mikio、Uemoto Shinji、Kawaguchi Yoshiya
    • Journal Title

      Scientific Reports

      Volume: 8 Pages: 15812-15812

    • DOI

      10.1038/s41598-018-34093-4

    • NAID

      120006715479

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exocrine tissue-driven TFF2 prevents apoptotic cell death of endocrine lineage during pancreas organogenesis2019

    • Author(s)
      Hirata Koji、Kodama Sota、Nakano Yasuhiro、Minaki-Nakagawa Yasuko、Aoyama Yoshiki、Sakikubo Morito、Goto Toshihiko、Yoshida Masahiro、Masui Toshihiko、Yamamoto Takuya、Uemoto Shinji、Kawaguchi Yoshiya
    • Journal Title

      Scientific Reports

      Volume: 9 Pages: 1636-1636

    • DOI

      10.1038/s41598-018-38062-9

    • NAID

      120006557515

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo reprogramming drives Kras-induced cancer development2018

    • Author(s)
      Hirofumi Shibata, Shingo Komura, Yosuke Yamada, Nao Sankoda, Akito Tanaka, Tomoyo Ukai, Mio Kabata, Satoko Sakurai, Bunya Kuze, Knut Woltjen, Hironori Haga, Yatsuji Ito, Yoshiya Kawaguchi, Takuya Yamamoto, Yasuhiro Yamada
    • Journal Title

      nature Communications

      Volume: 9 Pages: 2081-2081

    • DOI

      10.1038/s41467-018-04449-5

    • NAID

      120006473761

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms?After Curative Resection: A Single-Institution Analysis2018

    • Author(s)
      Masui Toshihiko、Sato Asahi、Nakano Kenzo、Uchida Yuichiro、Yogo Akitada、Anazawa Takayuki、Nagai Kazuyuki、Kawaguchi Yoshiya、Takaori Kyoichi、Uemoto Shinji
    • Journal Title

      Annals of Surgical Oncology

      Volume: 25 Pages: 528-534

    • DOI

      10.1245/s10434-017-6260-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abdominal contamination with Candida albicans after pancreaticoduodenectomy is related to hemorrhage associated with pancreatic fistulas2017

    • Author(s)
      Sato Asahi、Masui Toshihiko、Nakano Kenzo、Sankoda Nao、Anazawa Takayuki、Takaori Kyoichi、Kawaguchi Yoshiya、Uemoto Shinji
    • Journal Title

      Pancreatology

      Volume: 17 Pages: 484-489

    • DOI

      10.1016/j.pan.2017.03.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor2017

    • Author(s)
      Sato Asahi、Masui Toshihiko、Sankoda Nao、Nakano Kenzo、Uchida Yuichiro、Anazawa Takayuki、Takaori Kyoichi、Kawaguchi Yoshiya、Uemoto Shinji
    • Journal Title

      Surgical Case Reports

      Volume: 3 Pages: 1-5

    • DOI

      10.1186/s40792-017-0361-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement2017

    • Author(s)
      Masui T、Takaori K、Anazawa T、Sato A、Nakano K、Uchida Y、Yogo A、Goto Y、Matsumoto S、Kodama Y、Kanai M、Isoda H、Mizumoto M、Kawaguchi Y、Shibuya K、Itasaka S、Uemoto S
    • Journal Title

      Anticancer Research

      Volume: 37 Pages: 7023-7030

    • DOI

      10.21873/anticanres.12172

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] 膵立体構築における細胞間相互作用2019

    • Author(s)
      川口義弥
    • Organizer
      第119回日本外科学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の性質や特徴2018

    • Author(s)
      川口義弥
    • Organizer
      1からわかるiPS細胞
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた腸管組織の作成2018

    • Author(s)
      川口義弥
    • Organizer
      第17回京大病院iPS細胞・再生医学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Non-cell autonomous regulation in pancreatic organogenesis, regeneration and cancer2017

    • Author(s)
      Yoshiya Kawaguchi
    • Organizer
      CDB symposium 2017
    • Place of Presentation
      Kobe
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 膵臓の発生・再生・がんにおける細胞自律的・非自律的制御2017

    • Author(s)
      川口義弥
    • Organizer
      第25回北摂四医師会 北摂糖尿病フォーラム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵臓の発生・再生・がんにおける細胞非自律的制御機構2017

    • Author(s)
      川口義弥
    • Organizer
      東海医学会講演会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵臓の発生・再生・がんにおける細胞拳動制御機構2017

    • Author(s)
      川口義弥
    • Organizer
      J-PALS Conference 2017
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた糖尿病治療法開発の展望2017

    • Author(s)
      川口義弥
    • Organizer
      第5回石川県1型糖尿病シンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた立体的膵組織の作成2017

    • Author(s)
      川口義弥
    • Organizer
      日本ペインクリニック学会第51回大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 多様性幹細胞を用いた糖尿病治療開発の展望2017

    • Author(s)
      川口義弥
    • Organizer
      変革する糖尿病治療2017 in Kyoto
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵臓の発生・再生・癌における細胞非自律的制御機構2017

    • Author(s)
      川口義弥
    • Organizer
      Molecular Cardiovascular Metabolic Conference
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた新規糖尿病治療法開発2017

    • Author(s)
      川口義弥
    • Organizer
      平成29年度AMED再生医療・研究交流会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた糖尿病治療開発の展望2017

    • Author(s)
      川口義弥
    • Organizer
      患者さんにとって最適な糖尿病治療について考える会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵臓の発生・再生・がんにおける細胞非自律的制御機構2017

    • Author(s)
      川口義弥
    • Organizer
      "第55回日本糖尿病学会九州地方会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた立体的膵組織作成2017

    • Author(s)
      川口義弥
    • Organizer
      第17回日本先進糖尿病治療研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた糖尿病治療法開発の展望2017

    • Author(s)
      川口義弥
    • Organizer
      ヤング公開スクール大阪’17
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 多能性幹細胞を用いた立体的膵組織の作成2017

    • Author(s)
      川口義弥
    • Organizer
      第229回医学セミナー
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2022-11-04  

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