Reconstitution of totipotent nuclei in a test tube

2023 Fiscal Year Final Research Report

• Project Area: Program of totipotency: From decoding to designing
• Project/Area Number: 19H05755
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Shintomi Keishi 国立研究開発法人理化学研究所, 開拓研究本部, 専任研究員 (60462694)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: 受精 / 核移植 / 染色体 / カエル卵抽出液 / 再構成

Outline of Final Research Achievements

In a fertilized egg of animals, the regulatory mode of the gamete genome is converted to an early embryo-specific one, thus allowing differentiation into various cells in the whole body. In this study, we have examined mechanistically how factors derived from egg cytoplasm promote nuclear reprogramming.　Our attempt to modify cell-free assays of frog egg extracts revealed the role of proteins essential for zygotic genome activation and somatic cell nuclear transfer. We also established the protocols for in vitro reconstitution of these processes using purified factors. In sum, these results undoubtedly broaden our biochemical understanding of the process of totipotency acquisition.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

近年のゲノム科学的手法の飛躍的な進展により、核の再プログラム化に伴うエピゲノム変化への理解は飛躍的に進んだ一方で、再プログラム化を実行する卵由来のタンパク質の同定やその機能解析は大きく遅れている。また、体細胞核移植によるクローン作出が実用化されているにもかかわらず、その成功率は依然として低いままである。本研究で得られた成果は、これらの未解決の課題に対して、生化学的視点から解答をもたらすものである。