Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Peripheral Mononuclear Cells in Patients With Ankylosing Spondylitis

• Published in: Frontiers in immunology Vol. 12; p. 760381
• Main Authors: Xu, Huixuan, Yu, Haiyan, Liu, Lixiong, Wu, Hongwei, Zhang, Cantong, Cai, Wanxia, Hong, Xiaoping, Liu, Dongzhou, Tang, Donge, Dai, Yong
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22-11-2021
• Subjects: Adult; ankylosing spondylitis; Chromatin Immunoprecipitation Sequencing; Female; Gene Expression; Humans; Immunology; Leukocytes, Mononuclear - cytology; Male; NFkB; RNA-Seq; Single-Cell Analysis; single-cell assaying transposase accessible chromatin sequencing; single-cell RNA sequencing; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - immunology; TNF signaling pathway; Transcription Factors - genetics; Young Adult; single-cell RNA sequencing; single-cell assaying transposase accessible chromatin sequencing; NFkB; ankylosing spondylitis; TNF signaling pathway
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.760381

Genetic studies on ankylosing spondylitis (AS) have identified more than 100 pathogenic genes. Building a bridge between these genes and biologically targeted therapies is the current research hotspot.
We integrated single-cell assaying transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to explore the key genes and related mechanisms associated with AS pathogenesis.
We identified 18 cell types in peripheral mononuclear cells from patients with AS and normal controls and summarized the cell-type-specific abnormal genes by scRNA-seq. Interestingly, we found that the pathogenic gene
involved in AS progression originated from CD8+ T cells. Moreover, we observed an abnormal tumor TNF pathway mediated by abnormal expression of
,
,
,
, and
, and scATAC-seq results confirmed the abnormal accessible binding sites of transcriptional factors
,
, and
. The final magnetic bead sorting and quantitative real-time PCR(RT-qPCR) confirmed that
,
,
, and
in CD8+ T cells differed in the AS group.
Our results revealed a possible mechanism by which
abnormally regulates
,
, and
and drives
progression, providing a novel perspective from a single cell point of view in AS.