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

Updated June 29, 2025

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.

Noah ZaitlenUniversity of California, Los Angelesnzaitlen@g.ucla.edu
Chun Jimmie YeUniversity of California, San Franciscojimmie.ye@ucsf.edu
Richard Perez1
M. Grace Gordon1
Meena Subramaniam2
Min Cheol Kim1
George Hartoularos1
Sasha Targ1
Yang Sun1
Anton Ogorodnikov1
Raymund Bueno1
Andrew Lu3
Mike Thompson3
Nadav Rappoport4
Andrew Dahl5
Cristina Lanata6
Mehrdad Matloubian1
Lenka Maliskova1
Serena Kwek1
Tony Li1
Michal Slyper7
Julia Waldman8
Danielle Dionne8
Orit Rozenblatt-Rosen7
Lawrence Fong1
Maria Dall’era1
Brunilda Balliu3
Aviv Regev7
Jinoos Yazdany1
Lindsey Criswell6
Noah Zaitlen3
Chun Jimmie Ye1
1University of California, San Francisco
2Immunai Inc.
3University of California, Los Angeles
4Ben-Gurion University of the Negev
5University of Chicago
6National Human Genome Research Institute
7Genentech
8Klarman Cell Observatory, Broad Institute
None

To reference this project, please use the following link:

https://explore.data.humancellatlas.dev.clevercanary.com/projects/9fc0064b-84ce-40a5-a768-e6eb3d364ee0

Supplementary links are provided by contributors and represent items such as additional data which can’t be hosted here; code that was used to analyze this data; or tools and visualizations associated with this specific dataset.

1.https://cellxgene.cziscience.com/collections/436154da-bcf1-4130-9c8b-120ff9a888f22.https://zenodo.org/record/4724043#.YldFAW7MJuU
GEO Series Accessions:
GSE137029, GSE174188
INSDC Study Accessions:
INSDC Project Accessions:

Atlas

None

Analysis Portals

CZ CELLxGENE
CZ CELLxGENE

Project Label

Single-cellRNA-seqrevealscelltype-specificmolecula

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

blood

Organ Part

blood

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

systemic lupus erythematosus

Disease Status (Donor)

systemic lupus erythematosus

Development Stage

100 development stages

Library Construction Method

10x 3' v2

Nucleic Acid Source

single cell

Paired End

false

File Format

fastq

Cell Count Estimate

Unspecified

Donor Count

261
fastq800 file(s)
HCA Data PortalHCA Data Portal
AboutHelpPrivacyContact
v2.20.4-57ba9d0-dcp52