Single-cell analysis of tumor heterogeneity arising from the evolution of cancer stem cells

2021 Fiscal Year Final Research Report

• Project Area: Integrated analysis and regulation of cellular diversity
• Project/Area Number: 17H06325
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: The University of Tokyo
• Principal Investigator: Akiyama Tetsu 東京大学, 定量生命科学研究所, 特任教授 (70150745)
• Co-Investigator(Kenkyū-buntansha): 林 寛敦 東京大学, 定量生命科学研究所, 特任助教 (30583215)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: 1細胞RNA-seq / がん微小環境 / 腫瘍内不均一性 / がん / がん幹細胞 / 造腫瘍能 / non-coding RNA

Outline of Final Research Achievements

1) We performed single cell RNA-seq (scRNA-seq) analysis of ovarian cancer tissues and identified a novel stem cell population common to four histologic types of ovarian cancer. 2) We identified genes that regulate serum-induced differentiation of glioblastoma stem cells. 3) scRNA-seq analysis of tumors from tumor-bearing mice treated with a new molecularly targeted drug developed in our laboratory revealed that the immune system in the tumor microenvironment is modulated to suppress tumor growth. Moreover, we have identified and characterized genes involved in the tumorgenicity of glioblastoma and colon cancer cells. We found that 4) the histone deacetylase SIRT2 is critical for the tumorgenicity of glioblastoma stem cells and 5) a novel long non-coding RNA, termed CALIC, plays an important role in colon cancer metastasis.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、組織を構成する細胞の多様性とその多様性の創出機構の分子基盤を解明するために1細胞RNA-seq解析を積極的に活用して進めてきた。その結果、従来のバルクの解析では見出すことが難しかったがん幹細胞の維持に重要な遺伝子の同定や同一組織内でのがん細胞の分化（EMTなど）過程の可視化、がん組織の進展に重要な新たな細胞集団の同定など、1細胞解析だからこそ可能な新規の知見を多数見出すことができた。また、がん細胞、がん幹細胞の造腫瘍能に重要な遺伝子を見出し、その機能を明らかにした。本研究によって、がんの本質の理解が進み新しいがんの治療法への道筋が開かれることが期待される。