GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307363/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307363GEOGSEfalse3D epigenomic landscape of human retinal pigment epithelium [CUT&Tag]Retinal pigment epithelium (RPE) serves as a vital guardian of visual function, with its dysfunction driving pathogenesis in various retinal diseases, including age-related macular degeneration and inherited retinal disorders. While ongoing RPE cells transplantation clinical trials worldwide, the absence of standardized quality metrics for stem cell-derived RPE represents a significant gap. In this study, we aim to systematically dissect epigenomic divergence among human primary RPE (hRPE), induced pluripotent stem cell-derived RPE (iPSC-RPE), and immortalized ARPE-19 cells through multi-omic analyses. Our study elucidated the distinct functional characteristics of the three types of RPE and their underlying epigenetic regulatory mechanisms, with a particular focus on the development and functional maturation of iPSC-RPE. We further revealed cell-type-specific regulatory blueprints: hRPE exhibits strong extracellular matrix (ECM) organization capacity through 3D-epigenomic (3D genome folding and epigenomic state) regulation, as exemplified by the enrichment of the RUNX1 motif, whereas iPSC-RPE retains signatures of RPE development and weak ECM function, marked by transcription factors such as Hand1, OTX2, PAX6, and ECM-associated genes. On the other hand, ARPE-19 exhibits greater cell proliferation ability and specifically regulated by transcription factors such as KLF5. Together, our data greatly advance our understanding of RPE biology and provide a robust foundation for optimizing iPSC-RPE differentiation protocols and developing innovative therapeutic strategies for retinal diseases.2026/07/26GSE307363GSM9222844GSM9883418GSM9222822GSM9883419GSM9222823GSM9222842GSM9222820GSM9222821GSM9222843GSM9222840GSM9222841GSM9222819GSM9222839GSM9222817GSM9222818GSM9222815GSM9222837GSM9222838GSM9222816GSM9222835GSM9222813GSM9222836GSM9222814GSM9222833GSM9222834GSM9222831GSM9222832GSM9222830GSM9883412GSM9222828GSM9883413GSM9222829GSM9222826GSM9883414GSM9883415GSM9222827GSM9222824GSM9883416GSM9222825GSM988341724676307363Homo sapiens