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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 29, 2023 |
| Title |
Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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
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| Contributor(s) |
Amiri M, Tahmasebi S, Sonenberg N |
| Citation(s) |
38159280 |
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| Submission date |
Nov 27, 2023 |
| Last update date |
Apr 04, 2024 |
| Contact name |
Mehdi Amiri |
| E-mail(s) |
m.amiri.biology@gmail.com
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| Organization name |
McGill University
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| Department |
Biochemistry
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| Street address |
1160 Pine Avenue West
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| City |
Montreal |
| State/province |
Quebec |
| ZIP/Postal code |
H3A 1A3 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (12)
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| GSM7919152 |
mESC, WT, LIF2i, Rep3, RNA-Seq |
| GSM7919153 |
mESC, WT, LIF2i, Rep2, RNA-Seq |
| GSM7919154 |
mESC, WT, LIF2i, Rep1, RNA-Seq |
| GSM7919155 |
mESC, WT, LIF, Rep3, RNA-Seq |
| GSM7919156 |
mESC, WT, LIF, Rep2, RNA-Seq |
| GSM7919157 |
mESC, WT, LIF, Rep1, RNA-Seq |
| GSM7919158 |
mESC, KI, LIF2i, Rep3, RNA-Seq |
| GSM7919159 |
mESC, KI, LIF2i, Rep2, RNA-Seq |
| GSM7919160 |
mESC, KI, LIF2i, Rep1, RNA-Seq |
| GSM7919161 |
mESC, KI, LIF, Rep3, RNA-Seq |
| GSM7919162 |
mESC, KI, LIF, Rep2, RNA-Seq |
| GSM7919163 |
mESC, KI, LIF, Rep1, RNA-Seq |
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| This SubSeries is part of SuperSeries: |
| GSE248729 |
Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells |
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| Relations |
| BioProject |
PRJNA1045659 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248725_raw_read_count_rnaseq.csv.gz |
462.6 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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