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| Status |
Public on Jan 24, 2020 |
| Title |
Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Autoimmune uveoretinitis is a significant cause of visual loss, and mouse models offer unique opportunities to study its disease mechanisms. Aire-/- mice fail to express self-antigens in the thymus, exhibit reduced central tolerance, and develop a spontaneous, chronic, and progressive uveoretinitis. Using single-cell RNA sequencing (scRNA-seq), we characterized wild type and Aire-/- retinas to define, in a comprehensive and unbiased manner, the cell populations and gene expression patterns associated with disease. Based on scRNA-seq, immunostaining, and in situ hybridization, we infer that (i) the dominant effector response in Aire-/- retinas is Th1-driven, (ii) a subset of monocytes convert to either a macrophage/microglia state or a dendritic cell state, (iii) the development of tertiary lymphoid structures constitutes part of the Aire-/- retinal phenotype, (iv) all major resident retinal cell types respond to Interferon gamma by changing their patterns of gene expression, and (v) Muller glia up-regulate specific genes in response to Interferon gamma and may act as antigen presenting cells.
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| Overall design |
Single-cell RNAseq of AireKO and age- and sex-matched WT retinas. For AireKO retinas, two replicates for Grade 2 disease and two replicates for Grade 3 disease were used.
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| Contributor(s) |
Heng JS, Hackett SF, Stein-O'Brien GL, Winer BL, Williams J, Campochiaro PA, Goff LA, Nathans J |
| Citation(s) |
31843893 |
| Submission date |
Jun 05, 2019 |
| Last update date |
Jan 24, 2020 |
| Contact name |
Jacob S Heng |
| E-mail(s) |
jacob.heng@outlook.com
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| Organization name |
Johns Hopkins University School of Medicine
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| Department |
Molecular Biology and Genetics
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| Lab |
Nathans Lab
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| Street address |
725 North Wolfe Street
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21210 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA546561 |
| SRA |
SRP200499 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132229_RAW.tar |
178.1 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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