Understanding of totipotency through characterization of interactions between transposable elements and early embryos

2023 Fiscal Year Final Research Report

• Project Area: Program of totipotency: From decoding to designing
• Project/Area Number: 19H05753
• 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: Keio University
• Principal Investigator: Siomi Haruhiko 慶應義塾大学, 医学部(信濃町), 教授 (60202107)
• Project Period (FY): 2019-06-28 – 2024-03-31
• Keywords: PIWI / piRNA / ハムスター / トランスポゾン / 初期胚発生 / ZGA

Outline of Final Research Achievements

Result 1: Many animals have a conserved adaptive genome defence system known as the Piwi-interacting RNA (piRNA) pathway, which is essential for germ cell development and function. Disruption of individual mouse Piwi genes results in male but not female sterility, leading to the assumption that PIWI genes play little or no role in mammalian oocytes. With an improved high-quality genome assembly and annotation of golden hamster, we were able to generate PIWI-defective golden hamsters, which have defects in the production of functional oocytes.
Result 2: Zygotic genome activation (ZGA) is a critical step that promotes totipotency. MERVL is transiently upregulated during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remained elusive. We were able to demonstrate that MERVL expression is essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

ハムスターをモデル動物として使用するための基盤整備を行い、PIWI遺伝子の変異がメスの不妊につながることを世界ではじめて証明した。これはヒト女性の不妊の原因としてPIWI遺伝子の変異がゲノム解析の対象となるきっかけとなった。
一方、以前より哺乳類初期杯においてトランスポゾンが高発現することが知られていたがその機能は不明であった。私達は多コピー遺伝因子の発現を抑制する手法を開発し、マウス初期杯において高発現するトランスポゾンMERVLを抑制したところ、胚発生が停止した。これは着床前胚においてトランスポゾンの発現が胚発生に不可欠であることを示した世界で初めての例となった。