2025-04-10 京都大学iPS細胞研究所
<関連情報>
- https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/250410-100000.html
- https://www.science.org/doi/10.1126/sciadv.adq5484
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
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.