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Series GSE248724 Query DataSets for GSE248724
Status Public on Dec 29, 2023
Title Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells [Ribo-Seq]
Organism Mus musculus
Experiment type Other
Summary The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2αbecomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESC) is largely unexplored. We employ a multi-omics approachconsisting of ribosome profiling, proteomics, and metabolomics inwild-type(eIF2α+/+)andphosphorylation-deficient mutant eIF2α(eIF2αA/A)mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naïve pluripotency. We show a transient increase in p-eIF2α in the naïve epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins which govern pluripotency, chromatin organization, and glutathione synthesis.Thus, p-eIF2αacts as a key regulator of the naïve pluripotency gene regulatory network.
Overall design To delineate the mechanisms by which phosphorylation of eIF2α controls the naïve state of pluripotency, we performed ribosome profiling (Ribo-Seq) and RNA-Seq on eIF2αA/A (KI) and eIF2α+/+ (WT) mouse embryonic stem cells (mESCs) grown in LIF/2i and LIF conditions
Contributor(s) Amiri M, Tahmasebi S, Sonenberg N
Citation(s) 38159280
Submission date Nov 27, 2023
Last update date Apr 04, 2024
Contact name Mehdi Amiri
Organization name McGill University
Department Biochemistry
Street address 1160 Pine Avenue West
City Montreal
State/province Quebec
ZIP/Postal code H3A 1A3
Country Canada
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (20)
GSM7919132 mESC, WT, LIF2i, Rep3, Ribo-Seq
GSM7919133 mESC, WT, LIF2i, Rep2, Ribo-Seq (RNaseI)
GSM7919134 mESC, WT, LIF2i, Rep2, Ribo-Seq
This SubSeries is part of SuperSeries:
GSE248729 Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells
BioProject PRJNA1045657

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Supplementary file Size Download File type/resource
GSE248724_raw_read_count_riboseq.csv.gz 689.0 Kb (ftp)(http) CSV
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Raw data are available in SRA

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