翻訳開始因子EIF3Dはシグナル伝達経路のバランスを調整することで多能性幹細胞の自己複製を支える

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2025-04-10 京都大学iPS細胞研究所

京都大学iPS細胞研究所(CiRA)の大久保周子助教、高橋和利准教授らの研究チームは、ヒト多能性幹細胞(PSC)の自己複製維持に不可欠な翻訳開始因子EIF3Dを特定しました。EIF3Dは、複数のp53調節因子の翻訳を制御し、p53の発現を低く保つことで、PSCの未分化状態と高い増殖能を維持します。この研究は、翻訳制御がPSCの分化多能性維持メカニズムにおいて重要な役割を果たすことを示し、今後の幹細胞研究の新たな方向性を示唆しています。

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EIF3Dはヒトの始原多能性において重要なシグナル伝達経路のホメオスタシスを保護する EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency

Chikako Okubo, Michiko Nakamura, Masae Sato, Yuichi Shichino, […], and Kazutoshi Takahashi
Science Advances  Published:9 Apr 2025
DOI:https://doi.org/10.1126/sciadv.adq5484

翻訳開始因子EIF3Dはシグナル伝達経路のバランスを調整することで多能性幹細胞の自己複製を支える

Abstract

Although pluripotent stem cell (PSC) properties, such as differentiation and infinite proliferation, have been well documented within the frameworks of transcription factor networks, epigenomes, and signal transduction, they remain unclear and fragmented. Directing attention toward translational regulation as a bridge between these events can yield additional insights into previously unexplained mechanisms. Our functional CRISPR interference screen–based approach revealed that EIF3D, a translation initiation factor, is crucial for maintaining primed pluripotency. Loss of EIF3D disrupted the balance of pluripotency-associated signaling pathways, thereby compromising primed pluripotency. Moreover, EIF3D ensured robust proliferation by controlling the translation of various p53 regulators, which maintain low p53 activity in the undifferentiated state. In this way, EIF3D-mediated translation contributes to tuning the homeostasis of the primed pluripotency networks, ensuring the maintenance of an undifferentiated state with high proliferative potential. This study provides further insights into the translation network in maintaining pluripotency.

細胞遺伝子工学
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