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SRX22659181: GSM7919135: mESC, WT, LIF2i, Rep1, Ribo-Seq (RNaseI); Mus musculus; OTHER
1 ILLUMINA (Illumina NovaSeq 6000) run: 189.9M spots, 6.9G bases, 2.5Gb downloads

External Id: GSM7919135_r1
Submitted by: Biochemistry, McGill University
Study: Impact of eIF2a phosphorylation on the translational landscape of mouse embryonic stem cells [Ribo-Seq]
show Abstracthide Abstract
The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2abecomes 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(eIF2a+/+)andphosphorylation-deficient mutant eIF2a(eIF2aA/A)mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2a-dependent translational control of naïve pluripotency. We show a transient increase in p-eIF2a in the naïve epiblast layer of E4.5 embryos. Absence of eIF2a phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3a/ß) withdrawal. p-eIF2a controls translation of mRNAs encoding proteins which govern pluripotency, chromatin organization, and glutathione synthesis.Thus, p-eIF2aacts as a key regulator of the naïve pluripotency gene regulatory network. Overall design: To delineate the mechanisms by which phosphorylation of eIF2a controls the naïve state of pluripotency, we performed ribosome profiling (Ribo-Seq) and RNA-Seq on eIF2aA/A (KI) and eIF2a+/+ (WT) mouse embryonic stem cells (mESCs) grown in LIF/2i and LIF conditions
Sample: mESC, WT, LIF2i, Rep1, Ribo-Seq (RNaseI)
SAMN38457819 • SRS19654816 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM7919135
Instrument: Illumina NovaSeq 6000
Strategy: OTHER
Source: TRANSCRIPTOMIC
Selection: other
Layout: SINGLE
Construction protocol: Cells were washed twice with ice-cooled PBS containing 100 μg/mL CHX, and lysed. Lysates were incubated on ice for 10 min, followed by centrifugation at 16000 x g for 10 min at 4°C. A portion of supernatants was saved for RNA-Seq. Ribo-Seq samples were digested with MNase or RNAse I (Epicenter) and digested polysomes were loaded on a 10-50% sucrose density gradient and centrifuged at 36,000 rpm for 3 hours at 4°C. Fractions corresponding to monosome peak fractions were collected, pooled, and RNAs were extracted using Trizol. For Ribo-Seq library prep, we followed McGlincy and Ingolia 2017 ribosome profiling technique with some modification. RNA was electrochemically separated on a 15% TBU-Urea gel, and fragments of 25-40 nt were selected. After gel extraction, rRNA depletion, and dephosphorylation, ligation was performed with pre-adenylated linkers containing Unique Molecular Identifiers (UMIs) and barcodes. The ligated samples underwent gel purification, reverse transcription, and circularization using CircLigase I. Another rRNA depletion step was done before qPCR optimization. The final PCR product, confirmed for size and quantity, was sequenced on an Illumina NovaSeq 6000 System.
Runs: 1 run, 189.9M spots, 6.9G bases, 2.5Gb
Run# of Spots# of BasesSizePublished
SRR26965535189,881,6966.9G2.5Gb2023-12-29

ID:
30671976

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