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Three-dimensional imaging and morphometric analysis on proliferation of pseudo-biliary tracts and differentiation into cholangiocarcinomas

Research Project

Project/Area Number 15K19025
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pathological medical chemistry
Research InstitutionKyushu University

Principal Investigator

TAKASHIMA Yasuo  九州大学, 生体防御医学研究所, 特任助教 (50621083)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords肝内胆管癌 / 分化転換 / Notchシグナル / Kupffer細胞 / アポトーシス / 肝前駆細胞 / LIN28B / miRNA / 障害肝モデルマウス / 細胆管反応 / 3Dイメージ / ヒト肝細胞癌 / 遠隔転移 / マイクロRNA
Outline of Final Research Achievements

For chronic diseases and cancers in liver, it is desirable to diagnose the three-dimensional (3D) structures of lesions and altered microtubule structures on a single cell-based observation. In this study, we purpose to develop technical infrastructures for pathological diagnosis and basic medicine, based on morphometrics for proliferation of pseudo-biliary tracts and cholangiocarcinomas, derived from pseudo-biliary epithelial cells differentiated from hepatocytes, using a high-resolution digital 3D reconstruction. Here we showed that Kupffer cells, known as stellate macrophages, stimulate Notch signaling in hepatocytes surrounding central veins, therefore, hepatocytes can be reprogrammed into bile duct-like cells without apoptosis. We also demonstrated that LIN28B, in hepatoblasts, suppresses tumor suppressive miRNAs including miR-125a/b and let-7b, and maintains expression of LIN28B itself, thereby, regulating their proliferation and suppressing differentiation into biliary cells.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (3 results)

All 2016

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

  • [Journal Article] Kupffer cells induce Notch-mediated hepatocyte conversion in a common mouse model of intrahepatic cholangiocarcinoma2016

    • Author(s)
      Terada M., Horisawa K., Miura S., Takashima Y., Ohkawa Y., Sekiya S., Matsuda-Ito K., Suzuki A.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 34691-34691

    • DOI

      10.1038/srep34691

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Suppression of let-7b and miR-125a/b maturation by Lin28b enables maintenance of stem cell properties in hepatoblasts2016

    • Author(s)
      Takashima Y, Terada M, Udono M, Miura S, Yamamoto J, Suzuki A
    • Journal Title

      Hepatology

      Volume: in press Issue: 1 Pages: 245-260

    • DOI

      10.1002/hep.28548

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 肝内胆管がんモデルマウスにおいて、クッパー細胞がNotchシグナルを活性化し、肝細胞の分化転換を誘導する2016

    • Author(s)
      寺田 茉衣子, 堀澤 健一, 三浦 静, 高島 康郎, 大川 恭行, 関谷 明香, 松田 花菜江, 鈴木 淳史
    • Organizer
      第23回肝細胞研究会
    • Place of Presentation
      大阪大学中之島センター
    • Year and Date
      2016-07-07
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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