Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration
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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.
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Müller cells are a major source of complement proteins in the inner retina.
“Müller cells are also considered a major source of complement proteins in the inner retina [115,130,277].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [115]
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- Authors
- Menon, M., Mohammadi, S., Davila-Velderrain, J., Goods, B. A., Cadwell, T. D., Xing, Y., Stemmer-Rachamimov, A., Shalek, A. K., Love, J. C., Kellis, M., & Hafler, B. P.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Hafler, Brian P.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-10-25
- Volume
- 10
- Issue
- 1
- Pages
- 4902-4902
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6814749
- OpenAlex
- W2981346196
- Cited by
- 331
- References
- 43
- Citations by year
- 2026: 36 · 2025: 45 · 2024: 56 · 2023: 42 · 2022: 70 · 2021: 50 · 2020: 30 · 2019: 1
- FWCI
- 12.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Nature
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (AI039671, EY026652)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- age-related macular degeneration, human retina, retinal cell types, single-cell transcriptomic atlas, macroglia, cone photoreceptors, gene expression signatures, retinal inflammation
- MeSH terms
- Astrocytes, Blood Vessels, Humans, Macular Degeneration, Neuroglia, Retina, Retinal Ganglion Cells, Retinal Vessels, Gene Expression, Sequence Analysis, RNA, Microglia, Retinal Rod Photoreceptor Cells, Retinal Cone Photoreceptor Cells, Genetic Predisposition to Disease, Gene Expression Profiling, Amacrine Cells, Retinal Bipolar Cells, Retinal Horizontal Cells, Retinal Neurons, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Ependymoglial Cells
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