Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration

• Published in: Nature communications 2019-10, Vol.10 (1), p.4902-9, Article 4902
• Main Authors: Menon, Madhvi, Mohammadi, Shahin, Davila-Velderrain, Jose, Goods, Brittany A., Cadwell, Tanina D., Xing, Yu, Stemmer-Rachamimov, Anat, Shalek, Alex K., Love, John Christopher, Kellis, Manolis, Hafler, Brian P.
• Format: Article
• Language: English
• Subjects: 13/62; 14/19; 14/32; 14/63; 38/39; 38/91; 631/378/2613/1786; 692/699/3161/1626; 82/51; Age; Age related diseases; Amacrine Cells - metabolism; Astrocytes - metabolism; Blindness; Blood Vessels; Complexity; Ependymoglial Cells - metabolism; Eye diseases; Gene Expression; Gene Expression Profiling; Gene sequencing; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genome-wide association studies; Genomes; Geriatrics; Glia; Heterogeneity; High-Throughput Nucleotide Sequencing; Humanities and Social Sciences; Humans; Macular degeneration; Macular Degeneration - genetics; Microglia - metabolism; multidisciplinary; Neuroglia - metabolism; Photoreceptors; Retina; Retina - cytology; Retina - metabolism; Retinal Bipolar Cells - metabolism; Retinal cells; Retinal Cone Photoreceptor Cells - metabolism; Retinal Ganglion Cells - metabolism; Retinal Horizontal Cells - metabolism; Retinal Neurons - metabolism; Retinal Rod Photoreceptor Cells - metabolism; Retinal Vessels - cytology; Retinal Vessels - metabolism; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sequence Analysis, RNA; Single-Cell Analysis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12780-8

Genome-wide association studies (GWAS) have identified genetic variants associated with age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. However, it has been challenging to identify the cell types associated with AMD given the genetic complexity of the disease. Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) of human retinas using two independent platforms, and report the first single-cell transcriptomic atlas of the human retina. Using a multi-resolution network-based analysis, we identify all major retinal cell types, and their corresponding gene expression signatures. Heterogeneity is observed within macroglia, suggesting that human retinal glia are more diverse than previously thought. Finally, GWAS-based enrichment analysis identifies glia, vascular cells, and cone photoreceptors to be associated with the risk of AMD. These data provide a detailed analysis of the human retina, and show how scRNA-seq can provide insight into cell types involved in complex, inflammatory genetic diseases. “Genome-wide association studies have identified variants associated with age-related macular degeneration (AMD); however, other than identifying this as a complement mediated inflammatory disease, little biology has emerged. Here, authors used novel computational tools from the Broad Institute to examine the relationship of single-cell transcriptomics and genome-wide association studies (GWAS) in the human retina and demonstrate that GWAS-associated risk alleles associated with AMD are enriched in glia and vascular cells and that human retinal glia are more diverse than previously thought