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Visualizing the Epigenetic Landscape of Aging and Cellular Reprogramming: Optimized ATAC-see for cells and tissues

ABSTRACT: Spatial chromatin organization dictates cellular function and resilience, yet scalable imaging methods to quantify chromatin states in situ across aging and interventions are lacking. While ATAC-see can visualize accessible chromatin, its broader application is hindered by protocol variability, low throughput, and incompatibility with complex tissues. Here, we systematically optimize the ATAC-see workflow for robust, high-throughput quantitative imaging in fixed, adherent mammalian cells and fresh-frozen tissues. We validate the platform's sensitivity to pharmacologic remodeling and apply it to replicative, chronological, and pathological aging in primary human fibroblasts, revealing progressive age-associated chromatin opening and heterochromatin remodeling. Furthermore, we demonstrate that our optimized ATAC-see captures rapid, reversible chromatin reorganization during OSK(M)-driven partial reprogramming of aged fibroblasts. Finally, we extend a cost-effective and accessible protocol to murine tissue sections, quantifying in situ age-dependent remodeling. This standardized framework establishes chromatin accessibility as a highly scalable, sequencing-compatible imaging biomarker for evaluating aging and rejuvenation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE338065 | GEO | 2026/07/31

REPOSITORIES: GEO

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