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

Madhvi Menon,Yu Xing,Jose Davila-Velderrain,Anat Stemmer-Rachamimov,Tanina D Cadwell,Brittany A Goods,Manolis Kellis,John Christopher Love,Shahin Mohammadi,Alex K Shalek,Brian P Hafler

doi:10.1038/s41467-019-12780-8

Abstract

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.

Highlights

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
Following preprocessing and quality control (Supplementary Table 2), a total of 20,091 and 3,248 cells were retained for further analysis from the microfluidics and Seq-Well platforms, respectively
Using a recently developed algorithm, archetypal-analysis for cell-type identification (ACTION)[11], we extracted a set of underlying cell states, termed archetypes that explain transcriptional heterogeneity with increasing resolution

Summary

Introduction

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. Prior studies of the human retina have defined cell types based on morphology, function, or the expression of a limited number of genes[3].

Results

Conclusion