| Literature DB >> 35389781 |
Richard K Perez1, M Grace Gordon2,3,4,5, Meena Subramaniam2,4, Min Cheol Kim1,3,4,6,7, George C Hartoularos2,3,4, Sasha Targ1,2,6, Yang Sun3,4, Anton Ogorodnikov3,4, Raymund Bueno3,4, Andrew Lu8, Mike Thompson9, Nadav Rappoport10, Andrew Dahl11, Cristina M Lanata3,12, Mehrdad Matloubian3,12, Lenka Maliskova4,13, Serena S Kwek14, Tony Li14, Michal Slyper15, Julia Waldman15, Danielle Dionne15, Orit Rozenblatt-Rosen15, Lawrence Fong14, Maria Dall'Era1, Brunilda Balliu16, Aviv Regev15,17,18, Jinoos Yazdany3, Lindsey A Criswell3,4,12, Noah Zaitlen19, Chun Jimmie Ye3,4,12,13,20,21,22.
Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and states associated with SLE remains incomplete. We profiled more than 1.2 million peripheral blood mononuclear cells (162 cases, 99 controls) with multiplexed single-cell RNA sequencing (mux-seq). Cases exhibited elevated expression of type 1 interferon-stimulated genes (ISGs) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell type-specific expression features predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data to map cell type-specific cis-expression quantitative trait loci and to link SLE-associated variants to cell type-specific expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.Entities:
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Year: 2022 PMID： 35389781 PMCID： PMC9297655 DOI： 10.1126/science.abf1970
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714