Reprogramming associated point mutations and ROS

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H03615
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: National Institutes for Quantum and Radiological Science and Technology
• Principal Investigator: ARAKI RYOKO 国立研究開発法人量子科学技術研究開発機構, 放射線医学総合研究所 放射線障害治療研究部, グループリーダー(定常) (40392211)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ゲノム初期化 / 変異 / iPS細胞 / 全ゲノムシーケンシング

Outline of Final Research Achievements

Thus far, presence of a significant number of mutations has been reported in iPS cell genomes. In this study, we aimed to understand the mechanism which causes these numerous mutations and develop a method to generate iPS cells with few mutations. In this study, we demonstrated that the initial stage of genome reprogramming is radio resistance. Further analyses revealed a overexpression of CyclinD1 and a deficiency of cell cycle check point function occur in a transient manner during the initial stage of genome reprogramming. Importantly, it was showed that the point mutations in iPS cell genomes accumulate just in the initial stage. In addition, we here also discovered that iPS cells established from human cord blood-derived erythroblasts had a mutation frequency of 1/5 to 1/10 of the frequency observed in previous iPS cells.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

ゲノム初期化のメカニズムの理解、更にiPS細胞を用いた再生医療研究への貢献が期待される。