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Single-cell RNA-seq reveals cell type-specific molecular and genetic associations to lupus.
Perez, Richard K; Gordon, M Grace; Subramaniam, Meena; Kim, Min Cheol; Hartoularos, George C; Targ, Sasha; Sun, Yang; Ogorodnikov, Anton; Bueno, Raymund; Lu, Andrew; Thompson, Mike; Rappoport, Nadav; Dahl, Andrew; Lanata, Cristina M; Matloubian, Mehrdad; Maliskova, Lenka; Kwek, Serena S; Li, Tony; Slyper, Michal; Waldman, Julia; Dionne, Danielle; Rozenblatt-Rosen, Orit; Fong, Lawrence; Dall'Era, Maria; Balliu, Brunilda; Regev, Aviv; Yazdany, Jinoos; Criswell, Lindsey A; Zaitlen, Noah; Ye, Chun Jimmie.
Afiliação
  • Perez RK; School of Medicine, University of California, San Francisco, CA, USA.
  • Gordon MG; Biological and Medical Informatics Graduate Program, University of California, San Francisco, CA, USA.
  • Subramaniam M; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Kim MC; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Hartoularos GC; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
  • Targ S; Biological and Medical Informatics Graduate Program, University of California, San Francisco, CA, USA.
  • Sun Y; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Ogorodnikov A; School of Medicine, University of California, San Francisco, CA, USA.
  • Bueno R; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Lu A; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Thompson M; Medical Scientist Training Program, University of California, San Francisco, CA, USA.
  • Rappoport N; UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.
  • Dahl A; Biological and Medical Informatics Graduate Program, University of California, San Francisco, CA, USA.
  • Lanata CM; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Matloubian M; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Maliskova L; School of Medicine, University of California, San Francisco, CA, USA.
  • Kwek SS; Biological and Medical Informatics Graduate Program, University of California, San Francisco, CA, USA.
  • Li T; Medical Scientist Training Program, University of California, San Francisco, CA, USA.
  • Slyper M; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Waldman J; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Dionne D; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Rozenblatt-Rosen O; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Fong L; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Dall'Era M; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Balliu B; UCLA-Caltech Medical Scientist Training Program, Los Angeles, CA, USA.
  • Regev A; Department of Computer Science, University of California, Los Angeles, CA, USA.
  • Yazdany J; Department of Software and Information Systems Engineering, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
  • Criswell LA; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
  • Zaitlen N; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
  • Ye CJ; Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA, USA.
Science ; 376(6589): eabf1970, 2022 04 08.
Article em En | MEDLINE | ID: mdl-35389781
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Lúpus Eritematoso Sistêmico Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Science Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interferon Tipo I / Lúpus Eritematoso Sistêmico Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Science Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
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