{"doi":"10.1016/j.celrep.2023.113615","title":"Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells","abstract":"The integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2α becomes 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 (ESCs) is largely unexplored. We employ a multi-omics approach consisting of ribosome profiling, proteomics, and metabolomics in wild-type (eIF2α +/+ ) and phosphorylation-deficient mutant eIF2α (eIF2α A/A ) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naive pluripotency. We show a transient increase in p-eIF2α in the naive 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 that govern pluripotency, chromatin organization, and glutathione synthesis. Thus, p-eIF2α acts as a key regulator of the naive pluripotency gene regulatory network.","journal":"Cell Reports","year":2023,"id":335796,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260650,"name":"Stephen J. Kiniry","orcid":"0000-0001-5913-7093","position":1,"is_corresponding":false},{"id":260652,"name":"Anthony Possemato","orcid":"0000-0001-7484-5549","position":2,"is_corresponding":false},{"id":1048663,"name":"Niaz Mahmood","orcid":"0000-0003-4018-5516","position":3,"is_corresponding":false},{"id":1066265,"name":"Tayebeh Basiri","orcid":null,"position":4,"is_corresponding":false},{"id":935816,"name":"Catherine R. Dufour","orcid":"0000-0001-7324-3458","position":5,"is_corresponding":false},{"id":936419,"name":"Negar Tabatabaei","orcid":null,"position":6,"is_corresponding":false},{"id":1065772,"name":"Qiyun Deng","orcid":"0000-0002-6900-2587","position":7,"is_corresponding":false},{"id":1065773,"name":"Michael A. Bellucci","orcid":"0000-0002-1539-7245","position":8,"is_corresponding":false},{"id":1065774,"name":"Keerthana Harwalkar","orcid":"0000-0003-1713-4294","position":9,"is_corresponding":false},{"id":261611,"name":"Matthew P. Stokes","orcid":null,"position":10,"is_corresponding":false},{"id":861496,"name":"Vincent Giguère","orcid":"0000-0001-9567-3694","position":11,"is_corresponding":false},{"id":250288,"name":"Randal J. Kaufman","orcid":"0000-0003-4277-316X","position":12,"is_corresponding":false},{"id":971925,"name":"Yojiro Yamanaka","orcid":"0000-0003-1483-8691","position":13,"is_corresponding":false},{"id":17938,"name":"Pavel V. Baranov","orcid":"0000-0001-9017-0270","position":14,"is_corresponding":false},{"id":477449,"name":"Soroush Tahmasebi","orcid":"0000-0002-2807-5480","position":15,"is_corresponding":false},{"id":17875,"name":"Nahum Sonenberg","orcid":"0000-0002-4707-8759","position":16,"is_corresponding":false},{"id":1050766,"name":"Mehdi Amiri","orcid":"0000-0002-8646-2649","position":0,"is_corresponding":true}],"reference_count":106,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:02.777338Z","pmid":"38159280","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}