GEO series

Decoupling oxidative resilience from reprogramming to rejuvenate the RPE and restore vision [GSTA4_ATAC-seq_1]

GSE304037 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 42 samples Submitted 2026/06/11 Platform GPL24247

Summary

OCT4, SOX2, and KLF4 (OSK) Yamanaka factors can reverse age-related epigenetic changes, yet alternate mechanisms by which they promote tissue resilience remain poorly understood. Oxidative stress contributes to retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. Here, we show that OSK expression in RPE promotes Tet2-independent oxidative resilience through acute, memory-free transcriptomic changes, and restores visual function in aged mice. Integrative functional genomics helped identify GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a key OSK downstream effector. OSK directly and dynamically activates GSTA4, recapitulating a stem cell-derived stress resilience program. GSTA4 overexpression alone enhances oxidative resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline while avoiding OSK’s pleiotropic effects. GSTA4 is upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis directly regulated by OSK, that can be decoupled from reprogramming, providing a framework for developing more precise rejuvenation therapies.

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Direct links to NCBI, no account and no request form: the whole study as GSE304037_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 42 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1298818 and SRA study SRP604796. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

9 conditions, mostly with about 5 replicates each

15-months ×5 24-months ×5 15-months-OSK ×5 24-months-OSK ×5 15-months-OSK-onoff ×5 3-months ×4 3-months-OSK ×4 3-months-OSK-onoff ×4 +1 more

Supports a between-group comparison across 40 samples.

9 replicated groups read from the first 40 of 42 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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