{"doi":"10.1101/2025.09.24.678136","title":"Differentiation stage-specific use of cap-independent and cap-dependent translation initiation in hematopoiesis","abstract":"Abstract Cell stress can increase the use of m 7 G-cap-independent, IRES-mediated translation initiation relative to cap-dependent translation (IRES/Cap). Reporters that quantify IRES/Cap have demonstrated differential activity across cultured cell types and stress conditions. By generating an IRES/Cap reporter mouse, we were able to systematically evaluate IRES/Cap across distinct tissues and cell types during physiological stresses and lineage commitment. Caloric stress invoked the expected boost in IRES/Cap translation regardless of differentiation state, but unexpectedly IRES/Cap progressively increased during hematopoietic and epithelial (hair follicle) differentiation under normal, homeostatic conditions. This was independent of total protein output or cell cycle. Even within cells of a given differentiation state, cells with lower relative-IRES utilization had markedly higher multipotent capability in vivo . The RNA processing protein PTBP1 is a mediator of this translation initiation preference. Therefore, low IRES/Cap is a signature of high stemness and suggests modulation of translation initiation participates in cell differentiation state.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575845,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1484043,"name":"Ting Zhao","orcid":"0000-0003-4195-1884","position":1,"is_corresponding":false},{"id":1278829,"name":"Anna Kiem","orcid":"0009-0005-1177-1374","position":2,"is_corresponding":false},{"id":1240200,"name":"Trine Kristiansen","orcid":"0000-0002-2703-2438","position":3,"is_corresponding":false},{"id":2684,"name":"Karin Gustafsson","orcid":"0000-0002-2440-1269","position":4,"is_corresponding":false},{"id":500244,"name":"Lai Ping Wong","orcid":null,"position":5,"is_corresponding":false},{"id":289464,"name":"Emily Scott-Solomon","orcid":"0000-0002-7018-2132","position":6,"is_corresponding":false},{"id":259609,"name":"Marissa Fahlberg","orcid":"0000-0002-2597-7147","position":7,"is_corresponding":false},{"id":908592,"name":"Sarah Forward","orcid":null,"position":8,"is_corresponding":false},{"id":1039673,"name":"Emane Rose Assita","orcid":null,"position":9,"is_corresponding":false},{"id":663876,"name":"Giulia Schiroli","orcid":"0000-0002-9812-8728","position":10,"is_corresponding":false},{"id":1279294,"name":"Maris Handley","orcid":null,"position":11,"is_corresponding":false},{"id":2682,"name":"Youmna Kfoury","orcid":"0000-0003-2495-3378","position":12,"is_corresponding":false},{"id":1484044,"name":"Tsuyoshi Fukushima","orcid":"0000-0002-9350-777X","position":13,"is_corresponding":false},{"id":1484045,"name":"Samuel D. 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