An interspecies barrier to tetraploid complementation and chimera formation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08623
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: Yamaguchi Tomoyuki 東京大学, 医科学研究所, 特任准教授 (80392158)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 異種間キメラ / 多能性幹細胞 / 発生

Outline of Final Research Achievements

To study development of the conceptus in xenogeneic environments, we assessed interspecies chimera formation as well as tetraploid complementation between mouse and rat. Overall contribution of donor PSC-derived cells was lower in interspecies chimeras than in intraspecies chimeras, and high donor chimerism was associated with anomalies or embryonic death. Organ to organ variation in donor chimerism was greater in interspecies chimeras than in intraspecies chimeras, suggesting species-specific affinity differences among interacting molecules necessary for organogenesis.
In interspecies tetraploid complementation, embryo development was near normal until the stage of placental formation, after which no embryos survived.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

異種間キメラの作製は動物体内での臓器作製法である胚盤胞補完法の基礎となる技術であり、多能性幹細胞が動物の発生過程に協調できるかどうかは臓器作製の可否に非常に重要な情報である。本研究で、多能性幹細胞は異種の発生環境に完全に協調できる訳ではなく、組織によって器官形成に重要な細胞間相互作用ができないという結果が得られた。多能性幹細胞が寄与できない異種組織では、細胞間相互作用に必要な分子の種を合わせるといった遺伝子改変が動物体内に多能性幹細胞由来の臓器を作製する上で必要となると考えられる。