{"doi":"10.1073/pnas.2007439117","title":"Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation","abstract":"-acetylglucosamine (O-GlcNAc), in NSCs promotes a glial fate switch. We detect an age-dependent decrease in NSC O-GlcNAc levels coincident with decreased neurogenesis and increased gliogenesis in the mature hippocampus. Mimicking an age-related loss of NSC O-GlcNAcylation in young mice reduces neurogenesis, increases astrocyte differentiation, and impairs associated cognitive function. Using RNA-sequencing of primary NSCs following decreased O-GlcNAcylation, we detected changes in the STAT3 signaling pathway indicative of glial differentiation. Moreover, using O-GlcNAc-specific mass spectrometry analysis of the aging hippocampus, together with an in vitro site-directed mutagenesis approach, we identify loss of STAT3 O-GlcNAc at Threonine 717 as a driver of astrocyte differentiation. Our data identify the posttranslational modification, O-GlcNAc, as a key molecular regulator of regenerative decline underlying an age-related NSC fate switch.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":54027,"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":109,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.964,"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":277058,"name":"Xuelai Fan","orcid":"0000-0001-5113-1092","position":1,"is_corresponding":false},{"id":277059,"name":"Jason C. Maynard","orcid":"0000-0001-7838-5420","position":2,"is_corresponding":false},{"id":277060,"name":"Elizabeth Wheatley","orcid":"0000-0001-5459-8827","position":3,"is_corresponding":false},{"id":277061,"name":"Gregor Bieri","orcid":"0000-0003-0737-231X","position":4,"is_corresponding":false},{"id":236132,"name":"Julien Couthouis","orcid":"0000-0002-2378-4595","position":5,"is_corresponding":false},{"id":256139,"name":"Alma L. Burlingame","orcid":"0000-0002-8403-7307","position":6,"is_corresponding":false},{"id":14929,"name":"Saul Villeda","orcid":"0000-0002-2726-9582","position":7,"is_corresponding":false},{"id":279705,"name":"Charles White","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-18T21:03:43.037640Z","pmid":"32848054","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":[]}