Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus-Reference-Cited by-同舟云学术

Single-cell RNA-seq reveals cell type–specific molecular and genetic associations to lupus

Published:2022-04-08 Issue:6589 Volume:376 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Perez Richard K.¹^ORCID,Gordon M. Grace²³⁴⁵^ORCID,Subramaniam Meena²⁴^ORCID,Kim Min Cheol¹³⁴⁶⁷^ORCID,Hartoularos George C.²³⁴^ORCID,Targ Sasha¹²⁶,Sun Yang³⁴^ORCID,Ogorodnikov Anton³⁴,Bueno Raymund³⁴^ORCID,Lu Andrew⁸^ORCID,Thompson Mike⁹^ORCID,Rappoport Nadav¹⁰^ORCID,Dahl Andrew¹¹^ORCID,Lanata Cristina M.³¹²^ORCID,Matloubian Mehrdad³¹²^ORCID,Maliskova Lenka⁴¹³^ORCID,Kwek Serena S.¹⁴^ORCID,Li Tony¹⁴^ORCID,Slyper Michal¹⁵^ORCID,Waldman Julia¹⁵^ORCID,Dionne Danielle¹⁵^ORCID,Rozenblatt-Rosen Orit¹⁵^ORCID,Fong Lawrence¹⁴^ORCID,Dall’Era Maria¹^ORCID,Balliu Brunilda¹⁶^ORCID,Regev Aviv¹⁵¹⁷¹⁸^ORCID,Yazdany Jinoos³^ORCID,Criswell Lindsey A.³⁴¹²,Zaitlen Noah¹⁹^ORCID,Ye Chun Jimmie³⁴¹²¹³²⁰^ORCID

Affiliation:

1. School of Medicine, University of California, San Francisco, CA, USA.

2. Biological and Medical Informatics Graduate Program, University of California, San Francisco, CA, USA.

3. Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.

4. Institute for Human Genetics, University of California, San Francisco, CA, USA.

5. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.

6. Medical Scientist Training Program, University of California, San Francisco, CA, USA.

7. UC Berkeley–UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.

8. UCLA-Caltech Medical Scientist Training Program, Los Angeles, CA, USA.

9. Department of Computer Science, University of California, Los Angeles, CA, USA.

10. Department of Software and Information Systems Engineering, Ben-Gurion University of the Negev, Be’er Sheva, Israel.

11. Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

12. Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA, USA.

13. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.

14. Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, CA, USA.

15. Klarman Cell Observatory, Broad Institute, Cambridge, MA, USA.

16. Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

17. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

18. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

19. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.

20. Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference74 articles.

1. The global burden of SLE: prevalence, health disparities and socioeconomic impact

2. Systemic lupus erythematosus

3. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients

4. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

5. Type I Interferon in Systemic Lupus Erythematosus and Other Autoimmune Diseases

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