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Investigation of the molecular mechanism underlying aging based on epigenome alterations in intestinal epithelial stem cells

Research Project

Project/Area Number 16K13051
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionKeio University

Principal Investigator

SAITO Yoshimasa  慶應義塾大学, 薬学部(芝共立), 准教授 (90360114)

Co-Investigator(Renkei-kenkyūsha) SATO Toshiro  慶應義塾大学, 医学部, 准教授 (70365245)
KANAI Yae  慶應義塾大学, 医学部, 教授 (00260315)
YAMAMOTO Naoki  慶應義塾大学, 理工学部, 准教授 (40513289)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords老化 / 加齢 / エピゲノム変化 / 腸管上皮幹細胞 / オルガノイド培養 / ステムセルエイジング / 腸管上皮 / 幹細胞 / エピゲノム
Outline of Final Research Achievements

To understand the molecular mechanism underlying aging, we established intestinal epithelial organoids derived from both young and aged mice and investigated gene expression profiles and epigenome alterations. We found that cell proliferation and tissue formation were significantly inhibited in intestinal epithelial organoids derived from aged mice. In addition, epigenetic modifications including suppression of Lgr5 by trimethylation of histone H3 lysine 27 induced suppression of Wnt signaling. These findings indicate that epigenome alterations may lead to disabilities of cell proliferation and tissue formation during the process of aging.

Report

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

    (16 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] Medical University of Vienna(オーストリア)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Bile acid metabolism regulated by the gut microbiota promotes non-alcoholic steatohepatitis-associated hepatocellular carcinoma in mice.2018

    • Author(s)
      Yamada S, Takashina Y, Watanabe M, Nagamine R, Saito Y, Kamada N, Saito H.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 11 Pages: 9925-9939

    • DOI

      10.18632/oncotarget.24066

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Induction of differentiation of intrahepatic cholangiocarcinoma cells to functional hepatocytes using an organoid culture system2018

    • Author(s)
      Saito Yoshimasa、Nakaoka Toshiaki、Muramatsu Toshihide、Ojima Hidenori、Sukeda Aoi、Sugiyama Yuko、Uchida Ryoei、Furukawa Ryo、Kitahara Aya、Sato Toshiro、Kanai Yae、Saito Hidetsugu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 2821-2821

    • DOI

      10.1038/s41598-018-21121-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gut microbiota-mediated generation of saturated fatty acids elicits inflammation in the liver in murine high-fat diet-induced steatohepatitis.2017

    • Author(s)
      Yamada S, Kamada N, Amiya T, Nakamoto N, Nakaoka T, Kimura M, Saito Y, Ejima C, Kanai T, Saito H.
    • Journal Title

      BMC Gastroenterology

      Volume: 17 Issue: 1 Pages: 136-136

    • DOI

      10.1186/s12876-017-0689-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aberrant DNA Methylation as a Biomarker and a Therapeutic Target of Cholangiocarcinoma.2017

    • Author(s)
      Nakaoka T, Saito Y, Saito H.
    • Journal Title

      International Journal of Molecular Science

      Volume: 18 Issue: 6 Pages: 1111-1111

    • DOI

      10.3390/ijms18061111

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cluster microRNAs miR-194 and miR-215 suppress the tumorigenicity of intestinal tumor organoids.2017

    • Author(s)
      Nakaoka T, Saito Y, Shimamoto Y, Muramatsu T, Kimura M, Kanai Y, Saito H.
    • Journal Title

      Cancer Sci,

      Volume: 108 Issue: 4 Pages: 678-684

    • DOI

      10.1111/cas.13165

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A New Molecular Mechanism Underlying the Antitumor Effect of DNA Methylation Inhibitors via an Antiviral Immune Response.2017

    • Author(s)
      Saito Y, Nakaoka T, Saito H
    • Journal Title

      Advances in Protein Chemistry and Structural Biology

      Volume: 106 Pages: 227-242

    • DOI

      10.1016/bs.apcsb.2016.08.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] microRNA-mediated resistance to hypoglycemia in the HepG2 human hepatoma cell line.2016

    • Author(s)
      Ueki S, Murakami Y, Yamada S, Kimura M, Saito Y, Saito H
    • Journal Title

      BMC Cancer

      Volume: 16 Issue: 1 Pages: 732-732

    • DOI

      10.1186/s12885-016-2762-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.2016

    • Author(s)
      Saito Y, Nakaoka T, Sakai K, Muramatsu T, Toshimitsu K, Kimura M, Kanai T, Sato T, Saito H
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 25311-25311

    • DOI

      10.1038/srep25311

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Intrahepatic cholangiocarcinoma cells can be converted into functional hepatocytes by inhibition of Wnt signaling pathway.2017

    • Author(s)
      Saito Y, Nakaoka T, Muramatsu T, Kimura M, Saito H.
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2017
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腸管上皮オルガノイドにおけるエピゲノム変化に着目したステムセルエイジングの解明2017

    • Author(s)
      齋藤 義正、内田 諒英、村松 俊英、木村 真規、齋藤 英胤
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] オルガノイド培養技術による難治性がんのin vitroモデルの構築と創薬研究への応用2017

    • Author(s)
      齋藤 義正
    • Organizer
      第77回分析化学討論会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 胆管がんオルガノイドにおける糖欠乏下での幹細胞性の増強2017

    • Author(s)
      吉川 直、齋藤 義正、齋藤 英胤
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inhibition of DNA Methylation Suppresses Intestinal Tumor Organoids by Inducing an Anti-Viral Response.2016

    • Author(s)
      Saito Y, Sakai K, Muramatsu T, Nakaoka T, Kimura M, Saito H.
    • Organizer
      American Association for Cancer Research (AACR) Annual Meeting 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-04-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] Keio Research Highlights

    • URL

      https://research-highlights.keio.ac.jp/article/99/ancient-antiviral-response-could-help-treat-cancer

    • Related Report
      2017 Annual Research Report
  • [Remarks] がん幹細胞におけるエピゲノム異常を標的とした革新的な創薬研究

    • URL

      https://www.youtube.com/watch?v=QgmysbH_6_A&t

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2019-03-29  

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