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

• Main Authors: Mohammadi, Shahin (Author), Davila Velderrain, Jose (Author), Goods, Brittany A. (Author), Shalek, Alexander K (Author), Love, Christopher J. (Author), Kellis, Manolis (Author)
• Other Authors: Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory (Contributor), Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science (Contributor)
• Format: Article
• Language: English
• Published: Springer Science and Business Media LLC, 2020-05-28T18:14:35Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (Grant F32-AI136459)
National Institutes of Health (U.S.) (Grant U01-MH119509)
National Institutes of Health (U.S.) (Grant R01-AG062335)
National Institutes of Health (U.S.) (Grant U01-NS110453)