Single-nucleotide-polymorphism-adjacent super enhancer network mediates enhanced osteogenic differentiation of mesenchymal stem cells in ankylosing spondylitis [RNA-seq]
In order to recapitulated the primary mechanism of the pathologically enhanced osteogenesis of mesenchymal stem cells from ankylosing spondylitis patients (ASMSCs) over MSCs from healthy donor, we performed multiomic high-throughput sequencing. We analysed the H3K27ac ChIP-seq data according to ROSE algorithm, and identified super enhancers (SEs) in ASMSCs and HDMSCs. The ASMSC-unique SEs (ASUSEs) are associated with osteogenic differentiation and AS pathogenesis. By integrated analysis of H3K27ac ChIP-seq, ankylosing spondylitis (AS) SNPs and RNA-seq data, we discovered the transcription network regulated by AS SNP-adjacent super enhancers (SASEs) during the enhanced osteogenic differentiation of MSCs from AS patients (ASMSCs), which helped us gain insight into the crutial mechanism of AS pathological osteogenesis. And based on the inhibition effect of SE inhibitor JQ1 on the enhanced osteogenic differentiation of ASMSCs, we proposed that SEs may be attractive targets to treat AS pathological osteogenesis. Overall design: Examination of the mRNA profiles in ASMSCs and HDMSCs during osteogenic differentiation