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The translational landscape of ground state pluripotency

Author

Listed:
  • Yaser Atlasi

    (Radboud Institute for Molecular Life Sciences (RIMLS)
    Queen’s University Belfast)

  • Seyed Mehdi Jafarnejad

    (Queen’s University Belfast)

  • Christos G. Gkogkas

    (The University of Edinburgh)

  • Michiel Vermeulen

    (Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen)

  • Nahum Sonenberg

    (McGill University)

  • Hendrik G. Stunnenberg

    (Radboud Institute for Molecular Life Sciences (RIMLS)
    Princess Maxima Centre for Pediatric Oncology)

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.

Suggested Citation

  • Yaser Atlasi & Seyed Mehdi Jafarnejad & Christos G. Gkogkas & Michiel Vermeulen & Nahum Sonenberg & Hendrik G. Stunnenberg, 2020. "The translational landscape of ground state pluripotency," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15449-9
    DOI: 10.1038/s41467-020-15449-9
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