{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305868/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Mus musculus"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305868"],"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":"GSE305868","cross_references":{"GSM":["GSM9186482","GSM9186481","GSM9186480","GSM9186500","GSM9186501","GSM9186489","GSM9186488","GSM9186487","GSM9186486","GSM9186485","GSM9186484","GSM9186483","GSM9186513","GSM9186514","GSM9186515","GSM9186493","GSM9186492","GSM9186491","GSM9186490","GSM9186510","GSM9186511","GSM9186512","GSM9186479","GSM9186478","GSM9186477","GSM9186499","GSM9186498","GSM9186476","GSM9186475","GSM9186497","GSM9186474","GSM9186496","GSM9186495","GSM9186473","GSM9186494","GSM9186502","GSM9186503","GSM9186504","GSM9186505","GSM9186506","GSM9186507","GSM9186508","GSM9186509"],"GPL":["34290"],"GSE":["305868"],"taxon":["Mus musculus"]}}