Developmental regulation of genome stability in the germline stem cell cycle in mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02429
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43060:System genome science-related
• Research Institution: Kyoto University
• Principal Investigator: Chuma Shinichiro 京都大学, ウイルス・再生医科学研究所, 准教授 (20378889)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ゲノム / 遺伝 / 発生 / 生殖 / 幹細胞

Outline of Final Research Achievements

Genetic information is continuously modified by DNA damage and repair. In multicellular organisms, the genetic stability is differentially regulated depending on developmental stages and cell types. Among the various cell lineages, germline cells and stem cell systems are thought to maintain their genetic information more stably than differentiated somatic cells. However, how the genetic stability is properly coordinated with developmental programs is still not well understood. In this study, we carried out in depth comparative analyses of the genetic stability of mouse embryonic stem (ES) cells, their in vitro differentiated derivatives (ectoderm and mesendoderm etc), germline stem (GS) cells and embryonic fibroblasts etc. We obtained the proof of concept (POC) that the genetic stability of mouse embryonic stem cells can be artificially enhanced by modulating cell cycle activities and metabolic pathways while maintaining pluripotent differentiation capacities in vitro.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、個体発生の起点となる初期発生過程および生殖系列細胞の遺伝的安定性に関わる制御機構を明らかにする目的で、ES細胞、GS細胞、分化体細胞等のDNA損傷応答や染色体安定性に関わる詳細な比較データを得た。また、ES細胞の多能性を維持しつつ染色体安定性を人為的に向上する幾つかの特異的経路の候補を同定した。これらの結果は、発生生物学、遺伝学など基礎生物学的に重要なだけでなく、再生医科学領域等において期待が寄せられている幹細胞リソースの安定供給の為の技術開発の基盤となる事が期待される。