The translational landscape of ground state pluripotency

Nat Commun. 2020 Apr 1;11(1):1617. doi: 10.1038/s41467-020-15449-9.

Abstract

Translational control plays a central role in regulation of gene expression and can lead to significant divergence between mRNA- and protein-abundance. Here, we used genome-wide approaches combined with time-course analysis to measure the mRNA-abundance, mRNA-translation rate and protein expression during the transition of naïve-to-primed mouse embryonic stem cells (ESCs). We find that the ground state ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL) display higher ribosome density on a selective set of mRNAs. This set of mRNAs undergo strong translational buffering to maintain stable protein expression levels in 2iL-ESCs. Importantly, we show that the global alteration of cellular proteome during the transition of naïve-to-primed pluripotency is largely accompanied by transcriptional rewiring. Thus, we provide a comprehensive and detailed overview of the global changes in gene expression in different states of ESCs and dissect the relative contributions of mRNA-transcription, translation and regulation of protein stability in controlling protein abundance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation
  • Glycogen Synthase Kinase 3 / metabolism
  • Metabolic Networks and Pathways
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • Polyribosomes / genetics
  • Polyribosomes / metabolism*
  • Proteome / metabolism*
  • RNA, Messenger / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Transcriptome

Substances

  • Proteome
  • RNA, Messenger
  • Glycogen Synthase Kinase 3