{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304037/"]},"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=GSE304037"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Reprogramming Factors Activate a Non-Canonical Oxidative Resilience Pathway that Can Rejuvenate RPEs and Restore Vision [GSTA4_ATAC-seq]","description":"Oct4, Sox2, and Klf4 (OSK) Yamanaka factors induce pluripotency and reverse age-related epigenetic changes, yet the mechanisms by which they promote rejuvenation remain poorly explored. Oxidative stress contributes to CNS aging and retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. We find that OSK expression in RPE restores retinal structure and visual function in aged mice and promotes oxidative resilience through a non-canonical, Tet2-independent pathway. Integrative functional genomics identifies GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a necessary and sufficient OSK effector. Dynamic GSTA4 regulation by OSK recapitulates a stem cell derived stress resilience program. GSTA4 overexpression alone enhances mitochondrial resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline. GSTA4 is consistently upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis driven by Yamanaka factors that circumvents reprogramming, providing therapeutic insights for age-related diseases.","dates":{"publication":"2026/06/11"},"accession":"GSE304037","cross_references":{"GSM":["GSM9141454","GSM9141432","GSM9141453","GSM9141456","GSM9141434","GSM9141433","GSM9141455","GSM9141450","GSM9141472","GSM9141471","GSM9141452","GSM9141473","GSM9141451","GSM9141470","GSM9141469","GSM9141447","GSM9141468","GSM9141446","GSM9141449","GSM9141448","GSM9141465","GSM9141443","GSM9141442","GSM9141464","GSM9141445","GSM9141467","GSM9141466","GSM9141444","GSM9141461","GSM9141460","GSM9141463","GSM9141441","GSM9141462","GSM9141440","GSM9141439","GSM9141436","GSM9141458","GSM9141457","GSM9141435","GSM9141438","GSM9141459","GSM9141437"],"GPL":["24247"],"GSE":["304037"],"taxon":["Mus musculus"]}}