{"doi":"10.1084/jem.20200829","title":"The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function","abstract":"The mRNA N6-methyladenosine (m6A) modification has emerged as an essential regulator of normal and malignant hematopoiesis. Inactivation of the m6A mRNA reader YTHDF2, which recognizes m6A-modified transcripts to promote m6A-mRNA degradation, results in hematopoietic stem cell (HSC) expansion and compromises acute myeloid leukemia. Here we investigate the long-term impact of YTHDF2 deletion on HSC maintenance and multilineage hematopoiesis. We demonstrate that Ythdf2-deficient HSCs from young mice fail upon serial transplantation, display increased abundance of multiple m6A-modified inflammation-related transcripts, and chronically activate proinflammatory pathways. Consistent with the detrimental consequences of chronic activation of inflammatory pathways in HSCs, hematopoiesis-specific Ythdf2 deficiency results in a progressive myeloid bias, loss of lymphoid potential, HSC expansion, and failure of aged Ythdf2-deficient HSCs to reconstitute multilineage hematopoiesis. Experimentally induced inflammation increases YTHDF2 expression, and YTHDF2 is required to protect HSCs from this insult. Thus, our study positions YTHDF2 as a repressor of inflammatory pathways in HSCs and highlights the significance of m6A in long-term HSC maintenance.","journal":"The Journal of Experimental Medicine","year":2020,"id":51864,"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":146,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":87270,"name":"Louie N. van de Lagemaat","orcid":"0000-0002-2947-1557","position":1,"is_corresponding":false},{"id":260149,"name":"Hannah Lawson","orcid":"0000-0003-1450-1343","position":2,"is_corresponding":false},{"id":260150,"name":"Andrea Tavosanis","orcid":"0000-0003-3711-5904","position":3,"is_corresponding":false},{"id":260151,"name":"J Paris","orcid":"0000-0002-9416-6890","position":4,"is_corresponding":false},{"id":260152,"name":"Joana Campos","orcid":"0000-0001-8119-7607","position":5,"is_corresponding":false},{"id":260153,"name":"David Wotherspoon","orcid":"0000-0001-5094-1616","position":6,"is_corresponding":false},{"id":260154,"name":"Jozef Durko","orcid":"0000-0002-2395-8946","position":7,"is_corresponding":false},{"id":261477,"name":"Annika Sarapuu","orcid":null,"position":8,"is_corresponding":false},{"id":56482,"name":"Junho Choe","orcid":"0000-0002-2365-3755","position":9,"is_corresponding":false},{"id":260155,"name":"Ivayla Ivanova","orcid":"0000-0003-2949-9610","position":10,"is_corresponding":false},{"id":260156,"name":"Daniela S. Krause","orcid":"0000-0003-3603-1119","position":11,"is_corresponding":false},{"id":260157,"name":"Alex von Kriegsheim","orcid":"0000-0002-4952-8573","position":12,"is_corresponding":false},{"id":260158,"name":"Christian Much","orcid":"0000-0002-1644-8200","position":13,"is_corresponding":false},{"id":260159,"name":"Marcos Morgan","orcid":"0000-0002-3549-0375","position":14,"is_corresponding":false},{"id":260160,"name":"Richard I. Gregory","orcid":"0000-0001-8090-8673","position":15,"is_corresponding":false},{"id":260161,"name":"Adam J. Mead","orcid":"0000-0001-8522-1002","position":16,"is_corresponding":false},{"id":260162,"name":"Dónal O’Carroll","orcid":"0000-0002-8626-2217","position":17,"is_corresponding":false},{"id":260163,"name":"Kamil R. Kranc","orcid":"0000-0001-7547-4989","position":18,"is_corresponding":false},{"id":260148,"name":"Christopher Mapperley","orcid":"0000-0002-2059-7006","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T20:41:30.009880Z","pmid":"33156926","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":[]}