Translational and post-translational control of human nai spacing diaeresis ve versus primed pluripotency

Deciphering the regulatory network for human naive and primed pluripotency is of fundamental theoretical and applicable significance. Here, by combining quantitative proteomics, phosphoproteomics, and acetylproteomics analyses, we revealed RNA processing and translation as themost differentially regulated processes between naive and primed human embryonic stem cells (hESCs). Although glycolytic primed hESCs rely predominantly on the eukaryotic initiation factor 4E (eIF4E)-mediated cap-dependent pathway for protein translation, naive hESCs with reduced mammalian target of rapamycin complex (mTORC1) activity are more tolerant to eIF4E inhibition, and their bivalent metabolism allows for translating selective mRNAs via both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways to form a more compact naive proteome. Globally up-regulated proteostasis and down-regulated post-translational modifications help to further refine the naive proteome that is compatible with the more rapid cycling of naive hESCs, where CDK1 plays an indispensable coordinative role. These findings may assist in better understanding the unrestricted lineage potential of naive hESCs and in further optimizing conditions for future clinical applications

Automated summary

RNA processing and translation are identified as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs) through quantitative proteomics, phosphoproteomics, and acetylproteomics analyses. Naive hESCs have a more compact proteome and can translate selective mRNAs through both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways. These findings contribute to a better understanding of the potential of naive hESCs and the optimization of conditions for clinical applications.