{"doi":"10.1182/blood.2022016832","title":"Retinoid X receptor promotes hematopoietic stem cell fitness and quiescence and preserves hematopoietic homeostasis","abstract":"Hematopoietic stem cells (HSCs) balance self-renewal and differentiation to maintain hematopoietic fitness throughout life. In steady-state conditions, HSC exhaustion is prevented by the maintenance of most HSCs in a quiescent state, with cells entering the cell cycle only occasionally. HSC quiescence is regulated by retinoid and fatty-acid ligands of transcriptional factors of the nuclear retinoid X receptor (RXR) family. Herein, we show that dual deficiency for hematopoietic RXRα and RXRβ induces HSC exhaustion, myeloid cell/megakaryocyte differentiation, and myeloproliferative-like disease. RXRα and RXRβ maintain HSC quiescence, survival, and chromatin compaction; moreover, transcriptome changes in RXRα;RXRβ-deficient HSCs include premature acquisition of an aging-like HSC signature, MYC pathway upregulation, and RNA intron retention. Fitness loss and associated RNA transcriptome and splicing alterations in RXRα;RXRβ-deficient HSCs are prevented by Myc haploinsufficiency. Our study reveals the critical importance of RXRs for the maintenance of HSC fitness and their protection from premature aging.","journal":"Blood","year":2022,"id":245083,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9478,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":879493,"name":"Jesús Porcuna","orcid":"0000-0002-7423-9706","position":1,"is_corresponding":false},{"id":432588,"name":"Ramesh C. Nayak","orcid":"0000-0002-3206-8152","position":2,"is_corresponding":false},{"id":879494,"name":"Ana Paredes","orcid":"0000-0003-3119-8788","position":3,"is_corresponding":false},{"id":276878,"name":"Haixia Niu","orcid":"0000-0001-9282-5904","position":4,"is_corresponding":false},{"id":879495,"name":"Vanessa Núñez","orcid":"0000-0002-7473-1514","position":5,"is_corresponding":false},{"id":879496,"name":"Aditi Paranjpe","orcid":"0000-0002-3566-3993","position":6,"is_corresponding":false},{"id":312403,"name":"Manuel J. Gómez","orcid":"0000-0002-4111-4835","position":7,"is_corresponding":false},{"id":879497,"name":"Anukana Bhattacharjee","orcid":"0000-0002-4459-4926","position":8,"is_corresponding":false},{"id":315872,"name":"Daniel Schnell","orcid":null,"position":9,"is_corresponding":false},{"id":62255,"name":"Fátima Sánchez‐Cabo","orcid":"0000-0003-1881-1664","position":10,"is_corresponding":false},{"id":18433,"name":"John S. Welch","orcid":"0000-0001-6656-3672","position":11,"is_corresponding":false},{"id":229082,"name":"Nathan Salomonis","orcid":"0000-0001-9689-2469","position":12,"is_corresponding":false},{"id":432590,"name":"José A. Cancelas","orcid":"0000-0002-1291-7233","position":13,"is_corresponding":false},{"id":346901,"name":"Mercedes Ricote","orcid":"0000-0002-8090-8902","position":14,"is_corresponding":false},{"id":737071,"name":"María Piedad Menéndez-Gutierrez","orcid":"0000-0001-8045-2995","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T00:23:34.974895Z","pmid":"36347014","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":[]}