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

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.