Cellular diversity and hierarchy of colorectal cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K14620
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• 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)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 大腸がん / オルガノイド / 1細胞解析

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.

Free Research Field

細胞生物学

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。