The translational landscape of ground state pluripotency

Yaser Atlasi (), Seyed Mehdi Jafarnejad, Christos G. Gkogkas, Michiel Vermeulen, Nahum Sonenberg () and Hendrik G. Stunnenberg ()
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Yaser Atlasi: Radboud Institute for Molecular Life Sciences (RIMLS)
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)

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15449-9

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