Eif3d safeguards the homeostasis of Key signaling pathways in Human primed pluripotency

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.