Mapping systemic lupus erythematosus heterogeneity at the single-cell level

Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA sequencing, we profiled ~276,000 peripheral blood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 match...

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Published inNature immunology Vol. 21; no. 9; pp. 1094 - 1106
Main Authors Nehar-Belaid, Djamel, Hong, Seunghee, Marches, Radu, Chen, Guo, Bolisetty, Mohan, Baisch, Jeanine, Walters, Lynnette, Punaro, Marilynn, Rossi, Robert J., Chung, Cheng-Han, Huynh, Richie P., Singh, Prashant, Flynn, William F., Tabanor-Gayle, Joy-Ann, Kuchipudi, Navya, Mejias, Asuncion, Collet, Magalie A., Lucido, Anna Lisa, Palucka, Karolina, Robson, Paul, Lakshminarayanan, Santhanam, Ramilo, Octavio, Wright, Tracey, Pascual, Virginia, Banchereau, Jacques F.
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.09.2020
Nature Publishing Group
Subjects
631/250/38
692/699/249/1313/1613
Adolescent
Adult
Autoimmune diseases
Biomedical and Life Sciences
Biomedicine
Care and treatment
CD4 antigen
CD8 antigen
Cells, Cultured
Child
Children
Cohort Studies
Dendritic cells
Development and progression
Disease Progression
Female
Gene expression
Gene Expression Profiling
Genetic aspects
Genotype
Health aspects
Heterogeneity
Humans
Identification and classification
Immune response
Immunology
Infectious Diseases
Interferon
Interferons - genetics
Leukocytes (mononuclear)
Leukocytes, Mononuclear - physiology
Lupus
Lupus Erythematosus, Systemic - genetics
Lymphocytes B
Lymphocytes T
Male
Monocytes
Natural killer cells
Peripheral blood mononuclear cells
Plasma cells
Precision medicine
Resource
Ribonucleic acid
RNA
Sequence Analysis, RNA
Severity of Illness Index
Single-Cell Analysis - methods
Subpopulations
Systemic lupus erythematosus
Transcription
Transcriptome
Transcriptomes
United States
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Summary:Patients with systemic lupus erythematosus (SLE) display a complex blood transcriptome whose cellular origin is poorly resolved. Using single-cell RNA sequencing, we profiled ~276,000 peripheral blood mononuclear cells from 33 children with SLE with different degrees of disease activity and 11 matched controls. Increased expression of interferon-stimulated genes (ISGs) distinguished cells from children with SLE from healthy control cells. The high ISG expression signature (ISG hi ) derived from a small number of transcriptionally defined subpopulations within major cell types, including monocytes, CD4 + and CD8 + T cells, natural killer cells, conventional and plasmacytoid dendritic cells, B cells and especially plasma cells. Expansion of unique subpopulations enriched in ISGs and/or in monogenic lupus-associated genes classified patients with the highest disease activity. Profiling of ~82,000 single peripheral blood mononuclear cells from adults with SLE confirmed the expansion of similar subpopulations in patients with the highest disease activity. This study lays the groundwork for resolving the origin of the SLE transcriptional signatures and the disease heterogeneity towards precision medicine applications. Banchereau and colleagues provide a resource dataset that examines disease-related transcriptional profiles of peripheral whole-blood cells from adolescent patients with SLE by single-cell RNA-seq analysis.
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These authors jointly supervised this work
These two authors contributed equally
AUTHOR CONTRIBUTIONS
D.N.-B. processed the data, performed the analyses and wrote the manuscript. S.H. analyzed the data, performed the sub-cluster and patient stratification analysis and wrote the manuscript. R.M., handled the samples (with R.J.R., C-H.H. and R.P.H.) and performed flow experiments in cSLE and aSLE cohorts. G.C. helped D.N.-B. to analyzing the data. M.B. performed some of the cSLE single-cell experiments and preprocessing. P.S. helped interpreting the data. W-F.F. preprocessed some of the data. T.W. selected the cSLE patients. J.B. coordinated the study. L.W. collected the cSLE clinical data. O.R. and A.M. provided and selected the cHD controls. J-A.T-G. and N.K. collected the adult lupus samples, under the supervision of S.L. M.A.C. coordinated data acquisition and submission. A-L.L. helped editing the manuscript. J.F.B. and V.P. conceived, designed, supervised the study with O.R., P.R. and K.P., and wrote the manuscript with D.N.-B. All authors reviewed and approved the manuscript.
ISSN:1529-2908
1529-2916
DOI:10.1038/s41590-020-0743-0