Proteomics

Dataset Information

0

The translational landscape of naïve and primed state pluripotency


ABSTRACT: Translational control plays a central role in regulation of gene expression and can lead to significant divergence between mRNA- and protein-abundance. The translational landscape of early mammalian development and its impact on cellular proteome, however, remains largely un-explored. 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 into primed embryonic stem cells (ESCs). We found that the ground state ESCs cultured with GSK3- and MEK-inhibitors and LIF (2iL) display higher ribosome density on a selective set of mRNAs. These mRNAs show reduced translation during the exit from ground state pluripotency and transition to serum/LIF (SL) culture or upon commitment to primed epiblast-like stem cells (EpiLSCs). Strikingly, integrative analysis with cellular proteome indicate a strong translational buffering of this set of mRNAs in 2iL-ESCs leading to stable protein expression levels. Our data reveal that the global alteration of cellular proteome is largely accompanied by transcriptional rewiring. Furthermore, we identified a set of genes (including UHRF1 and KRAS) that undergo selective post-translational regulation during the transition of naïve into primed pluripotency and linked the observed changes to upstream GSK- and MEK/MAPK-signaling pathways using single inhibitor treated ESCs. Thus, we provide a comprehensive and detailed overview of the global changes in gene expression during the transition of naïve to primed pluripotency and dissect the relative contributions of RNA-transcription, translation and regulation of protein stability in controlling protein abundance.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus musculus  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Yaser Atlasi  

LAB HEAD: Henk Stunnenberg

PROVIDER: PXD014528 | Pride | 2020-04-03

REPOSITORIES: pride

altmetric image

Publications

The translational landscape of ground state pluripotency.

Atlasi Yaser Y   Jafarnejad Seyed Mehdi SM   Gkogkas Christos G CG   Vermeulen Michiel M   Sonenberg Nahum N   Stunnenberg Hendrik G HG  

Nature communications 20200401 1


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 se  ...[more]

Similar Datasets

2015-07-01 | E-GEOD-69356 | ArrayExpress
2015-07-01 | E-GEOD-69055 | ArrayExpress
| GSE78144 | GEO
2013-01-18 | E-GEOD-42580 | ArrayExpress
| GSE61994 | GEO
| GSE81494 | GEO
2019-07-04 | PXD011782 | Pride
2014-11-02 | E-GEOD-61997 | ArrayExpress
| GSE77622 | GEO
| GSE92273 | GEO