Gene-regulatory network analysis of ankylosing spondylitis with a single-cell chromatin accessible assay

Abstract

A detailed understanding of the gene-regulatory network in ankylosing spondylitis (AS) is vital for elucidating the mechanisms of AS pathogenesis. Assaying transposase-accessible chromatin in single cell sequencing (scATAC-seq) is a suitable method for revealing such networks. Thus, scATAC-seq was applied to define the landscape of active regulatory DNA in AS. As a result, there was a significant change in the percent of CD8+ T cells in PBMCs, and 37 differentially accessible transcription factor (TF) motifs were identified. T cells, monocytes-1 and dendritic cells were found to be crucial for the IL-17 signaling pathway and TNF signaling pathway, since they had 73 potential target genes regulated by 8 TF motifs with decreased accessibility in AS. Moreover, natural killer cells were involved in AS by increasing the accessibility to TF motifs TEAD1 and JUN to induce cytokine-cytokine receptor interactions. In addition, CD4+ T cells and CD8+ T cells may be vital for altering host immune functions through increasing the accessibility of TF motifs NR1H4 and OLIG (OLIGI and OLIG2), respectively. These results explain clear gene regulatory variation in PBMCs from AS patients, providing a foundational framework for the study of personal regulomes and delivering insights into epigenetic therapy.

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

“…Moreover, our scATAC-seq data confirmed the abnormal accessibility of FOS , JUN , and JUNB , which is consistent with a previous report ( 33 ). Interestingly, TNF , NFKB , FOS , JUN , and JUNB can construct a signaling pathway with upstream and downstream regulation.…”

“…For the analysis and verification of this regulatory network with genes and transcription factors, scATAC-seq analysis is a suitable method. Our group members have already recruited nine patients with AS and 12 healthy volunteers to perform scATAC-seq analysis in published articles ( 33 ). To integrate the data of scRNA-seq and scATAC-seq for correlation analysis and obtain further detailed information, we re-analyzed the original scATAC-seq data.…”

“…Yu ( 33 ) in our research team used a different clustering method (the method can be seen at: ) to analyze the scATAC sequencing library from 12 normal controls (NCs) and nine patients with AS. Among the seven different functional cell types, including NK cells, monocytes, memory CD4+ T cells, CD8+ T cells, B cells, and DCs, it was found that CD8+ T cells play an essential role in AS pathogenesis.…”

The Chromatin Accessibility Landscape of Peripheral Blood Mononuclear Cells in Patients With Systemic Lupus Erythematosus at Single-Cell Resolution

“…As described previously (11) and as described on the manufacturer's website https://support.10xgenomics.com/ single-cell-atac, scATAC-seq libraries were generated according to the Chromium Single Cell ATAC protocol (10x GENOMICS, CG000168). In brief, the isolated nuclei were incubated with the Transposition Mix.…”

DataSheet_1.docx

“…Yu (33) in our research team used a different clustering method (the method can be seen at: https://support. algorithms/overview) to analyze the scATAC sequencing library from 12 normal controls (NCs) and nine patients with AS.…”