Cellular diversity and hierarchy of colorectal cancer
| Project/Area Number |
16K14620
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
Yao Ryoji 公益財団法人がん研究会, がん研究所 細胞生物部, 部長 (80291095)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 大腸がん / オルガノイド / 1細胞解析 / 大腸がんオルガノイド / 一細胞解析 / 癌 |
|---|
| Outline of Final Research Achievements |
Cellular diversity of cancer tissue contributes to several biological aspects of cancer including resistance to chemotherapy. We have established patient-derived organoid from advanced colorectal cancer and have explored the cellular diversity. Single cell expression analysis (scRNA-seq) successfully identified five clusters determined by the distinct differentiation and proliferation markers. We have performed further detailed DE analysis, and have successfully identified the stem cell marker. The stem cells were visualized by genome editing of the organoid, and shown to have self-renew and multiple differentiation potentials. The ablation assay demonstrated that the stem cells were requited for efficient maintenance and growth of the organoids. These observations demonstrated the cellular diversity and hierarchy of cancer tissue and may provide the cue to develop efficient therapeutics.
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| Academic Significance and Societal Importance of the Research Achievements |
1細胞発現解析(scRNA-seq)により、進行大腸がん手術検体由来の三次元培養オルガノイドが、複数の細胞クラスターで構成されることが明らかになったことにより、がん組織の理解、さらにこれまで不可能であったヒトがん組織の解析が可能になった点で、高い学術的意義を有する。さらに、今後のがん治療法開発の理論的な根拠を与えることに加えて、オルガノイドが薬剤開発の研究リソースとして貢献できることを意味しており、社会的意義は大きい。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] TUFT1 interacts with RABGAP1 and regulates mTORC1 signaling2018
Author(s)
Kawasaki Natsumi、Isogaya Kazunobu、Dan Shingo、Yamori Takao、Takano Hiroshi、Yao Ryoji、Morishita Yasuyuki、Taguchi Luna、Morikawa Masato、Heldin Carl-Henrik、Noda Tetsuo、Ehata Shogo、Miyazono Kohei、Koinuma Daizo
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Journal Title
Cell Discovery
Volume: 4
Issue: 1
Pages: 1-16
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Suppression of intestinal tumors by targeting the mitotic spindle of intestinal stem cells.2016
Author(s)
1.Yao, R., Oyanagi, J. Natsume, Y. Kusama, D., Kato, Y., Nagayama, S. & Noda, T.
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Journal Title
Oncogene
Volume: Epub ahead of print
Issue: 47
Pages: 1-11
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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