Single cell profiling of GI cancer-initiating cells and their niche

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03656
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hayakawa Yoku 東京大学, 医学部附属病院, 講師 (60777655)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胃癌

Outline of Final Research Achievements

In this study, we molecularly examined the proliferation and expansion of gastric cancer-originating cells and the progression of cancer cells using mouse models and omics-analysis including single-cell level analysis and spatial analysis. Lineage tracing experiments revealed that epithelial stem cells are the main source of gastric cancer, and that dedifferentiation from mature differentiated cells such as chief cells hardly contributes to gastric cancer. Genetically engineered mice and single cell analysis showed that Rspo3/Lgr4 signals are important for proliferation and differentiation of stem cells. Investigation of a genetically modified model that develops gastric cancer revealed that gene mutations in tumor cells lead to high expression of characteristic molecules, which in turn causes remodeling of the surrounding microenvironment.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

胃癌発生段階における癌起源細胞とその周囲微小環境の変化の詳細解析により、胃発癌の分子学的メカニズムの一端が明らかになった。癌起源細胞とその周囲微小環境の変化を独自の遺伝子改変マウスの解析により、前癌病変・早期癌・浸潤癌・転移性癌の分子学的相違を明らかとなり、癌進行度別・サブタイプ別の病態理解が促進された。本解析によって得られたデータは、癌の予防および治療戦略を構築する上で極めて重要な新規創薬シーズとなると考えられる。