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| Status |
Public on Sep 20, 2020 |
| Title |
Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder affecting multiple organs, including eyes, skin, and central nervous system. It is known that monocytes significantly contribute to the development of autoimmune disease. However, the subset heterogeneity with unique functions and signatures in human circulating monocytes and the identity of disease-specific monocytic populations remain largely unknown. Here, we employed an advanced single-cell RNA sequencing technology to systematically analyze 11259 human circulating monocytes and genetically defined their subpopulations. We constructed a precise atlas of human blood monocytes，identified 6 subpopulations: including S100A12-; HLA-; CD16-; proinflammatory-; megakaryocyte-like-; and NK-like-monocytes subsets, and uncovered 2 previously unidentified subsets: HLA- and megakaryocyte-like monocyte subsets. Relative to healthy individuals, cellular composition, gene expression signatures, and activation states were markedly alternated in VKH patients utilizing cell type-specific programs, especially the CD16- and proinflammatory monocyte subpopulation. Notably, we discovered a disease-relevant subgroup, proinflammatory monocytes, which showed a discriminative gene expression signature indicative of inflammation, antiviral activity, and pathologic activation, and converted into pathologic activation state implicating the active inflammation during VKH disease. Additionally, we found the cell type-specific transcriptional signature of proinflammatory monocytes, ISG15, which could act as a disease biomarker to more accurately reflect disease activity and treatment response than symptom evaluation. Taken together, in this landmark study we present novel discoveries on accurate classification, molecular markers, and signaling pathways for VKH disease-associated monocytes and therapeutically targeting this proinflammatory monocyte subpopulation would provide an attractive approach for treating VKH as well as other autoimmune diseases.
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| Overall design |
10X single cell RNA-seq from 3 normal people and 3 VHK patient
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| Contributor(s) |
Hu Y, Xiao Y |
| Citation missing |
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| Submission date |
Apr 02, 2020 |
| Last update date |
Sep 22, 2020 |
| Contact name |
yuhua xiao |
| E-mail(s) |
xiaoyh26@mail2.sysu.edu.cn
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| Phone |
18728192414
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| Organization name |
Sun Yat-sen University
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| Department |
zhongshan Ophthalmic center
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| Street address |
jinsui load
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| City |
guangzhou |
| State/province |
guangdong province |
| ZIP/Postal code |
510627 |
| Country |
China |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA622822 |
| SRA |
SRP255078 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148020_RAW.tar |
295.5 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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