Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration
| Autor: | Madhvi Menon, Tanina D. Cadwell, Manolis Kellis, Brittany A. Goods, Yu Xing, Brian P. Hafler, Anat Stemmer-Rachamimov, J. C. Love, Jose Davila-Velderrain, Shahin Mohammadi, Alex K. Shalek |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Retinal Ganglion Cells Neuroglia/metabolism Retinal Ganglion Cells/metabolism genetic structures General Physics and Astronomy Gene Expression Genome-wide association study Retinal Horizontal Cells Astrocytes/metabolism Retinal Bipolar Cells/metabolism Transcriptome 0302 clinical medicine Single-cell analysis Retinal Rod Photoreceptor Cells lcsh:Science Multidisciplinary Macular Degeneration/genetics High-Throughput Nucleotide Sequencing 3. Good health medicine.anatomical_structure Retinal Neurons/metabolism Retinal Rod Photoreceptor Cells/metabolism Retinal Cone Photoreceptor Cells Microglia Single-Cell Analysis Neuroglia Retinal Neurons Amacrine Cells/metabolism Cell type Retinal Bipolar Cells Science Ependymoglial Cells Computational biology Biology Retinal Horizontal Cells/metabolism General Biochemistry Genetics and Molecular Biology Article Retina Microglia/metabolism 03 medical and health sciences Retina/cytology medicine Humans Genetic Predisposition to Disease Retinal Cone Photoreceptor Cells/metabolism Genetic association Sequence Analysis RNA Macular degeneration Gene Expression Profiling Retinal Vessels General Chemistry medicine.disease eye diseases Gene expression profiling Retinal Vessels/cytology 030104 developmental biology Amacrine Cells Astrocytes Blood Vessels lcsh:Q sense organs Ependymoglial Cells/metabolism 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-9 (2019) 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 2019, ' Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration ', Nature Communications, vol. 10, no. 1, pp. 4902 . https://doi.org/10.1038/s41467-019-12780-8 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-12780-8 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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