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Characterization of cellular heterogeneity of colon tumors by gene expression analyses at the single cell level

Research Project

Project/Area Number 26670195
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionNational Cancer Center Japan

Principal Investigator

Shiokawa Daisuke  国立研究開発法人国立がん研究センター, その他部局等, ユニット長 (90277278)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大腸がん / シングルセル / 遺伝子発現解析 / Wntシグナル
Outline of Final Research Achievements

In order to get an insight into the molecular basis of the tumor heterogeneity, we attempted to determine gene expression profiles of tumor cells at single cell levels. Colon adenomas as well as normal epithelium in mouse carcinogenesis models are single cell-sorted by flow cytometry, and the gene expression profiles of each cell were determined by RT-PCR assays (BioMark HD system, Fluidigm). By processing the resulting data by principal component analysis (PCA), we dissected the normal and tumor epithelium into stem and differentiated cell populations.
Notably, tumor-derived stem cells were located on distinct positions from those from normal colon on the PCA plot. Given the well-established roles of the Wnt pathway in colon cancer, we examined the expression of Wnt target genes, and found that the expression of a subset of Wnt targets was altered during carcinogenesis.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2015 2014

All Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Presentation] Heterogeneity of Lgr5-positive colon tumor stem cells demonstrated by single-cell qPCR2015

    • Author(s)
      Daisuke Shiokawa, Hirokazu Ohata, Koji Okamoto
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] Dynamic regulation of colon tumor-derived stem cells demonstrated by single-cell qPCR2015

    • Author(s)
      Daisuke Shiokawa, Hirokazu Ohata, Koji Okamoto
    • Organizer
      幹細胞シンポジウム
    • Place of Presentation
      東京大学 伊藤国際学術研究センターB2F 伊藤謝恩ホール
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Altered expression of a subset of Wnt target genes in colon tumor-derived stem cells demonstrated by single-cell qPCR2014

    • Author(s)
      Daisuke Shiokawa, Masako Ochiai, Hitoshi Nakagama, Koji Okamoto
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] ROS enhances stemness by activating mTOR pathway in colorectal cancer stem cells2014

    • Author(s)
      Hirokazu Ohata, Daisuke Shiokawa, Hitoshi Nakagama, Koji Okamoto
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] nterleukin-22 disrupts cell polarity and barrier function in the 3D cultured intestinal epithelial cell2014

    • Author(s)
      Yoshinori Ikarashi, Junya Asahira, Takuya Matsuyama, Daisuke Shiokawa, Kazuhiro Kato, Toshio Imai, Hitoshi Nakagama, and Koji Okamoto
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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