{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305926/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305926"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Epigenetic training licenses naïve CD8⁺ T cell metabolic fitness and function","description":"Naïve T cells maintain quiescence yet must respond rapidly to antigens, but how they prime this capacity is unclear. We identify histone variant H2A.Z as a key regulator of an epigenetic training program that licenses quiescent naïve CD8+ T cells for future activation. H2A.Z deficiency disrupts naïve T cell homeostasis and effector responses. Multi-omics reveals that H2A.Z is selectively deposited at OXPHOS gene promoters in quiescent naïve CD8+ T cells, priming the chromatin for rapid transcriptional induction. This training is developmentally instructed by tonic IL-7 signaling and regulated by transcription factor GABPα. Age-related decline in IL-7 signaling reduces H2A.Z occupancy and impairs T cell activation, while IL-7 supplementation or enforced H2A.Z expression rescues this defect. H2A.Z overexpression also enhances CAR-T cell stemness and antitumor efficacy. Our work defines an IL-7R–GABPα–H2A.Z–OXPHOS axis that epigenetically establishes metabolic and functional fitness in quiescent T cells, offering insights for immunotherapy targeting ageing and tumors.","dates":{"publication":"2026/08/10"},"accession":"GSE305926","cross_references":{"GSM":["GSM9188067","GSM9188089","GSM9188068","GSM9188069","GSM9188081","GSM9188082","GSM9188060","GSM9188061","GSM9188083","GSM9188084","GSM9188062","GSM9188085","GSM9188063","GSM9188064","GSM9188086","GSM9188087","GSM9188065","GSM9188088","GSM9188066","GSM9188080","GSM9188056","GSM9188078","GSM9188079","GSM9188057","GSM9188058","GSM9188059","GSM9188070","GSM9188092","GSM9188093","GSM9188071","GSM9188094","GSM9188072","GSM9188073","GSM9188051","GSM9188095","GSM9188096","GSM9188074","GSM9188052","GSM9188053","GSM9188097","GSM9188075","GSM9188076","GSM9188054","GSM9188098","GSM9188077","GSM9188055","GSM9188090","GSM9188091"],"GPL":["13112"],"GSE":["305926"],"taxon":["Mus musculus"]}}