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Multiplexed scRNA-seq reveals cellular and genetic correlates of SLE

ABSTRACT: Multiplexed scRNA-seq reveals cellular and genetic correlates of SLE

PROVIDER: PRJNA807046 | ENA |

REPOSITORIES: ENA

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Multiplexed scRNA-seq reveals cellular and genetic correlates of SLE

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Multiplexed scRNA-seq reveals the cellular and genetic correlates of systemic lupus erythematosus

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Multiplexed RNA-sequencing of 1M immune cells reveals the cellular, molecular, and genetic correlates of systemic lupus erythematosus

Project description: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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Longitudinal transcriptional pediatric SLE study with clinical parameters

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