Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration.
Madhvi Menon, Shahin Mohammadi, Jose Davila-Velderrain, Brittany A Goods, Tanina D Cadwell, Yu Xing, Anat Stemmer-Rachamimov, Alex K Shalek, John Christopher Love, Manolis Kellis, Brian P Hafler
Author Information
Madhvi Menon: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Shahin Mohammadi: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Jose Davila-Velderrain: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Brittany A Goods: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Tanina D Cadwell: Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA, 02115, USA.
Yu Xing: Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA, 02115, USA.
Anat Stemmer-Rachamimov: Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Alex K Shalek: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
John Christopher Love: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. ORCID
Manolis Kellis: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. ORCID
Brian P Hafler: Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. brian.hafler@yale.edu.
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.
