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| Status |
Public on Nov 10, 2019 |
| Title |
Multiplexed RNA-sequencing of 1M immune cells reveals the cellular, molecular, and genetic correlates of systemic lupus erythematosus |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Systemic lupus erythematosus (SLE) is an autoimmune disease defined by a broad range of symptoms that disproportionately affects women
Our knowledge of which immune cells mediate the etiology and pathogenesis of the disease remains incomplete
Identifying pathogenic cells using bulk gene expression analysis is confounded by the functional overlap and frequency variation of immune cell types
Here, we used multiplexed single-cell RNA-seq (scRNA-seq) to profile ~1 million peripheral blood mononuclear cells from 134 SLE cases and 58 healthy controls
Cases were marked by a reduction of naive CD4+ T cells, clonal restriction of effector memory CD8+ T cells, and elevated expression of interferon-stimulated genes in classical monocytes
An additional 15 cases experiencing active disease flares displayed increased expansion of effector memory CD8+ T cells and the presence of macrophages not seen in managed disease
Although cell-type-specific expression contributed most to inter-individual expression variability across all cells, cell composition accounted for more variability in genes differentially expressed in cases
We integrated dense genotyping data to map thousands of genetic variants, including SLE-associations, whose effects on expression are modified by cell type or interferon activation
Population-scale scRNA-seq analysis reveals changes in cell composition and state associated with SLE, and when integrated with genetic data, ascribes function to disease-associated and disease-modified variants
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| |
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| Overall design |
Multiplexed single cell sequencing of SLE patients and healthy controls
|
| |
|
| Contributor(s) |
Subramaniam M, Ye J |
| Citation(s) |
33127880 |
| Submission date |
Sep 06, 2019 |
| Last update date |
Apr 20, 2021 |
| Contact name |
Meena Subramaniam |
| E-mail(s) |
meena.s.subramaniam@gmail.com
|
| Organization name |
UCSF IHG
|
| Street address |
513 Parnassus Ave S-965
|
| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (66)
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| Relations |
| BioProject |
PRJNA564301 |
| SRA |
SRP220690 |
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