Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration
Andrew P. Voigt, Kelly Mulfaul, Nathaniel K. Mullin, Miles J. Flamme-Wiese, Joseph C. Giacalone, Edwin M. Stone, Budd A. Tucker, Todd E. Scheetz, Robert F. Mullins
Abstract
The human retinal pigment epithelium (RPE) and choroid are complex tissues that provide crucial support to the retina. Disease affecting either of these supportive tissues can lead to irreversible blindness in the setting of age-related macular degeneration. In this study, single-cell RNA sequencing was performed on macular and peripheral regions of RPE-choroid from 7 human donor eyes in 2 independent experiments. In the first experiment, total RPE/choroid preparations were evaluated and expression profiles specific to RPE and major choroidal cell populations were identified. As choroidal endothelial cells represent a minority of the total RPE/choroidal cell population but are strongly implicated in age-related macular degeneration (AMD) pathogenesis, a second single-cell RNA-sequencing experiment was performed using endothelial cells enriched by magnetic separation. In this second study, we identified gene expression signatures along the choroidal vascular tree, classifying the transcriptome of human choriocapillaris, arterial, and venous endothelial cells. We found that the choriocapillaris highly and specifically expresses the regulator of cell cycle gene (RGCC), a gene that responds to complement activation and induces apoptosis in endothelial cells. In addition, RGCC was the most up-regulated choriocapillaris gene in a donor diagnosed with AMD. These results provide a characterization of the human RPE and choriocapillaris transcriptome, offering potential insight into the mechanisms of choriocapillaris response to complement injury and choroidal vascular disease in age-related macular degeneration.
Datasets
1. Retina
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Source data
https://cellxgene.cziscience.com/collections/f8057c47-fcd8-4fcf-88b0-e2f930080f6e
Alias names
GSE135922, E-GEOD-135922, PMID31712411, PMC6883845
Cite this study
Voigt, A.P., Mulfaul, K., Mullin, N.K., Flamme-Wiese, M.J., Giacalone, J.C., Stone, E.M., Tucker, B.A., Scheetz, T.E. and Mullins, R.F., 2019. Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. Proceedings of the National Academy of Sciences, 116(48), pp.24100-24107. https://doi.org/10.1073/pnas.1914143116