{"doi":"10.7554/elife.85464","title":"O-GlcNAc glycosylation orchestrates fate decision and niche function of bone marrow stromal progenitors","abstract":"In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.","journal":"eLife","year":2023,"id":332241,"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":0.9566,"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":336102,"name":"Zan Huang","orcid":"0000-0001-8552-533X","position":1,"is_corresponding":false},{"id":355104,"name":"Mohamed E. Awad","orcid":"0000-0001-7525-5364","position":2,"is_corresponding":false},{"id":355106,"name":"Mohammed Elsalanty","orcid":"0000-0001-8185-8217","position":3,"is_corresponding":false},{"id":741002,"name":"James Cray","orcid":"0000-0002-8512-7005","position":4,"is_corresponding":false},{"id":361356,"name":"Lauren E. Ball","orcid":"0000-0001-6780-1679","position":5,"is_corresponding":false},{"id":277059,"name":"Jason C. Maynard","orcid":"0000-0001-7838-5420","position":6,"is_corresponding":false},{"id":256139,"name":"Alma L. Burlingame","orcid":"0000-0002-8403-7307","position":7,"is_corresponding":false},{"id":287643,"name":"Hu Zeng","orcid":"0000-0002-9909-7732","position":8,"is_corresponding":false},{"id":361558,"name":"Kim C. Mansky","orcid":"0000-0002-2826-5030","position":9,"is_corresponding":false},{"id":336104,"name":"Hai‐Bin Ruan","orcid":"0000-0002-3858-1272","position":10,"is_corresponding":false},{"id":336101,"name":"Zengdi Zhang","orcid":"0000-0003-2616-2262","position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T01:09:30.139849Z","pmid":"36861967","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":[]}