Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy

Zhongbo Jin, Wei Fan, Mark A. Jensen, Jessica M. Dorschner, George F. Bonadurer, Danielle M. Vsetecka, Shreyasee Amin, Ashima Makol, Floranne Ernste, Thomas Osborn, Kevin Moder, Vaidehi R Chowdhary, Timothy B Niewold

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objectives Important findings can be masked in gene expression studies of mixed cell populations. We examined single-cell gene expression in SLE patient monocytes in the context of clinical and immunological features. Methods Monocytes were purified from patients with SLE and controls, and individually isolated for single-cell gene expression measurement. A panel of monocyte-related transcripts were measured in individual classical (CL) and non-classical (NCL) monocytes. Results Analyses of both CL and NCL monocytes demonstrated that many genes had a lower expression rate in SLE monocytes than in controls. Unsupervised hierarchical clustering of the CL and NCL data sets demonstrated independent clusters of cells from the patients with SLE that were related to disease activity, type I interferon (IFN) and medication use. Thus, each of these factors exerted a different impact on monocyte gene expression that could be identified separately, and a number of genes correlated uniquely with disease activity. We found within-cell correlations between genes directly induced by type I IFN-induced and other non-IFN-induced genes, suggesting the downstream biological effects of type I IFN in individual human SLE monocytes which differed between CLs and NCLs. Conclusions In summary, single-cell gene expression in monocytes was associated with a wide range of clinical and biological features in SLE, providing much greater detail and insight into the cellular biology underlying the disease than previous mixed-cell population studies.

Original languageEnglish (US)
Article numbere000202
JournalLupus Science and Medicine
Volume4
Issue number1
DOIs
StatePublished - Aug 21 2017

Keywords

  • Autoimmunity
  • Cytokines
  • Systemic Lupus Erythematosus

ASJC Scopus subject areas

  • Immunology

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    Jin, Z., Fan, W., Jensen, M. A., Dorschner, J. M., Bonadurer, G. F., Vsetecka, D. M., Amin, S., Makol, A., Ernste, F., Osborn, T., Moder, K., Chowdhary, V. R., & Niewold, T. B. (2017). Single-cell gene expression patterns in lupus monocytes independently indicate disease activity, interferon and therapy. Lupus Science and Medicine, 4(1), [e000202]. https://doi.org/10.1136/lupus-2016-000202