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Transcriptomic and chromatin accessibility analysis of the human macular and peripheral retinal pigment epithelium at the single cell level.
American Journal of Pathology 2023 Februrary 11
Human retinal diseases are frequently characterized by pathology that is restricted to specific cell types and to specific regions of the eye. Several disease entities either selectively affect or spare the macula, the retinal region at the center of the posterior pole. Photoreceptor cells of the macula are responsible for high acuity vision and require metabolic support from non-neuronal cell types. Macular diseases often involve an epithelial cell layer known as the retinal pigment epithelium (RPE) that has several essential metabolic support functions for the overlying photoreceptors. In the current study, we probed how the RPE confers region-specific disease susceptibility by examining heterogeneity within human donor RPE. We profiled RPE nuclei from the macular and peripheral retina using joint single-cell RNA and ATAC sequencing. We found that the expression of several genes varies between macular and peripheral RPE. We further found region-specific ATAC peaks implying regulatory elements used exclusively by macular or peripheral RPE. Across anatomical regions, we identify subpopulations of RPE that appear to have differential expression levels of visual cycle genes. Finally, we examined loci connected to age related macular degeneration to better understand RPE-specific disease phenotypes. Together, these data show how gene expression regulation in the human RPE varies by region and subpopulation and provide a resource for better understanding the molecular basis of macular disease.
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