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Investigation of epigenetic modifications that specify tissue identity of adult epithelial cells

Research Project

Project/Area Number 18H02639
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49030:Experimental pathology-related
Research InstitutionKyoto University

Principal Investigator

Miyoshi Hiroyuki  京都大学, 医学研究科, 准教授 (30362479)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsエピジェネティクス / スフェロイド培養 / 組織幹細胞 / 癌幹細胞 / スフェロイド / がん幹細胞 / Wnt
Outline of Final Research Achievements

In this study, we investigated molecular and genetic mechanisms in which tissue and cancer stem cells specify their identity. Using a stem cell spheroid culture system, we demonstrated that transcriptional and epigenetic landscapes of normal tissue stem cells recapitulated their developmental stages. In colorectal cancer cells with low Wnt/beta-catenin signaling, cell growth and stemness were promoted partly by constitutive expression of MYC.

Academic Significance and Societal Importance of the Research Achievements

本研究で様々な組織から分離した上皮幹細胞を横断的に比較解析することにより、転写因子の組み合わせと強固なエピジェネティック修飾によって厳格に規定された臓器特異性の理解が進んだ。また、組織幹細胞の自家移植による組織修復の可能性が示された。
本研究で樹立した患者由来大腸がんスフェロイドは治療法開発のための有用な材料である。これらの培養でがん幹細胞が維持されるメカニズムを解明することにより、幹細胞性をターゲットとした治療戦略の開発が期待できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(5 results)

All 2020 2018 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) Remarks (3 results)

  • [Journal Article] Chemosensitivity of Patient-Derived Cancer Stem Cells Identifies Colorectal Cancer Patients with Potential Benefit from FGFR Inhibitor Therapy2020

    • Author(s)
      Yamamoto Takehito、Miyoshi Hiroyuki、Kakizaki Fumihiko、Maekawa Hisatsugu、Yamaura Tadayoshi、Morimoto Tomonori、Katayama Toshiro、Kawada Kenji、Sakai Yoshiharu、Taketo M. Mark
    • Journal Title

      Cancers

      Volume: 12 Pages: 2010-2010

    • DOI

      10.3390/cancers12082010

    • NAID

      120006888015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 高効率で低コストの患者由来大腸がんスフェロイド培養法2018

    • Author(s)
      三好 弘之
    • Organizer
      日本癌学会総会
    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学医学部附属病院先端医療研究開発機構 大腸がん新個別化治療プロジェクト

    • URL

      https://www4.mfour.med.kyoto-u.ac.jp/indexjp.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 京都大学医学部附属病院臨床研究総合センター(iACT) 大腸がん新個別化治療プロジェクト

    • URL

      https://www4.mfour.med.kyoto-u.ac.jp/researchjp.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 京都大学医学研究科遺伝薬理学ユニット 研究内容

    • URL

      http://www4.mfour.med.kyoto-u.ac.jp/researchjp.html

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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