​Science｜Single-cell omics analysis of systemic lupus erythematosus

AuthorNovember Systemic lupus erythematosus (Systemic lupus erythematosus, SLE) is a very complex and heterogeneous autoimmune disease, characterized by a systemic rash, severe joint erosion and even kidney failure
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Systemic lupus erythematosus has a higher incidence in Asian, African, and Spanish ancestry, and is more likely to occur in women [1-2]
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A large number of transcriptome analysis showed that the increased signal transduction of type I interferon, abnormal lymphocyte activation process, and failure to clear apoptotic cells in patients were the hallmarks of systemic lupus erythematosus [3]
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At the same time, various studies have found more than 100 gene loci associated with the occurrence of systemic lupus erythematosus
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However, the existing database is based on batch cell transcriptome analysis, so the current comprehensive census of circulating immune cells in systemic lupus erythematosus is still incomplete, and the key cell types and corresponding genetic associations are not clear
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To this end, the research group of Chun Jimmie Ye of the University of California, San Francisco, and the research group of Noah Zaitlen of the University of California, Los Angeles jointly published a paper in Science entitled Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus.
The method of single-cell RNA-seq (Multiplexed scRNA-seq, mux-seq) sequencing analysis has uncovered a "comprehensive census" map of systemic lupus erythematosus at the single-cell resolution level in a relatively economical way, providing a basis for this complex The treatment of autoimmune diseases provides new ideas
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The traditional study of circulating immune cells in systemic lupus erythematosus is mainly through flow cytometry sorting followed by quantitative analysis of different cell surface markers
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However, the problem with flow cytometry sorting is that it is biased, because it relies on limited cell markers, and the results obtained by batch cell transcriptome analysis do not have sufficient resolution to detect different cell type specificity.
Sexual expression differences
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Therefore, the authors hope that single-cell RNA-sequencing analysis of peripheral blood mononuclear cells (PBMCs) can characterize the cellular composition of the circulating immune system and the specific transcriptional states of cell types
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The authors obtained 264 SLE-related samples from California, which corresponded to 162 SLE cases and 99 healthy controls, and analyzed more than 1.
2 million peripheral blood single-cell cells in total (Figure 1)
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Figure 1.
Analysis of cell types in patients with systemic lupus erythematosus The authors found that the cell types obtained in the samples could be divided into 23 groups, divided into 16 subgroups
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Compared with controls, there were significant differences in the composition and transcriptional status of peripheral blood mononuclear cells in patients with systemic lupus erythematosus
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By analyzing lymphocytes, the authors found a decrease in naïve CD4+ T cells and an increase in the number of restricted GZMH+CD8+ T cells
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In addition, through transcriptome analysis of different cell types, it was found that the expression levels of I IFN-stimulated genes were significantly increased in patients, which was consistent with previous studies
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Using the established peripheral blood mononuclear cell atlas, the authors found that specific expression in different cell types can accurately predict the status of patients in vivo, and can use this to classify patients into different subtypes
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In addition, the authors mapped shared specific cis-quantitative shape loci among the 8 associated key cell types, which facilitates identification and analysis of different SLE types and fine mapping of disease-associated loci, At the same time, the authors discovered and identified a new systemic lupus erythematosus-associated locus
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Figure 2 Working model Overall, this work performed single-cell RNA-sequencing analysis of peripheral blood mononuclear cells from patients with systemic lupus erythematosus in a cost-effective manner, further revealing the heterogeneity of disease-related manifestations and treatment response and The need for molecular biology characterization and characterization
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Using mux-seq phylotype analysis, the authors analyzed changes in cell composition and specific transcriptional signatures of different cell types in patients with systemic lupus erythematosus, and annotated genetically associated loci for clinical research and Drug development provides a new database of resources
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Original link: https://doi.
org/10.
1126/science.
abf1970 Publisher: Eleven References 1.
E.
Carter, SG Barr, AE Clarke, The global burden of SLE: Prevalence, health disparities and socioeconomic impact.
Nat .
Rev.
Rheumatol.
12, 605–620 (2016).
doi: 10.
1038/nrrheum.
2016.
137; pmid: 275586592.
A.
Kaul et al.
, Systemic lupus erythematosus.
Nat.
Rev.
Dis.
Primers 2, 16039 (2016) .
doi: 10.
1038/nrdp.
2016.
39; pmid: 273066393.
R.
Banchereau et al.
, Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.
Cell 165, 551–565 (2016).
doi: 10.
1016/j.
cell.
2016.
03.
008; pmid: 27040498 Instructions for reprinting [Original article] BioArt original articles are welcome to forward and share, and reprinting is prohibited without permission.
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