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Mapping systemic lupus erythematosus heterogeneity at the single-cell level.

Djamel Nehar-Belaid | Seunghee Hong | Radu Marches | Guo Chen | Mohan Bolisetty | Jeanine Baisch | Lynnette Walters | Marilynn Punaro | Robert J Rossi | Cheng-Han Chung | Richie P Huynh | Prashant Singh | William F Flynn | Joy-Ann Tabanor-Gayle | Navya Kuchipudi | Asuncion Mejias | Magalie A Collet | Anna Lisa Lucido | Karolina Palucka | Paul Robson | Santhanam Lakshminarayanan | Octavio Ramilo | Tracey Wright | Virginia Pascual | Jacques F Banchereau
Nature immunology | 2020

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 (ISGhi) 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.

Pubmed ID: 32747814

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: U01 AI131386
  • Agency: NCI NIH HHS, United States
    Id: P30 CA034196
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI082715
  • Agency: NIAMS NIH HHS, United States
    Id: P50 AR070594
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI144301

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bcl2fastq (tool)

RRID:SCR_015058

Conversion software that both demultiplexes data and converts BCL files generated by Illumina sequencing systems to standard FASTQ file formats for downstream analysis.

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Seurat (tool)

RRID:SCR_016341

Software as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.

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