Academic Journal
SNP-adjacent super enhancer network mediates enhanced osteogenic differentiation of MSCs in ankylosing spondylitis
| العنوان: | SNP-adjacent super enhancer network mediates enhanced osteogenic differentiation of MSCs in ankylosing spondylitis |
|---|---|
| المؤلفون: | Yu, Wenhui, Chen, Keng, Ye, Guiwen, Wang, Shan, Wang, Peng, Li, Jinteng, Zheng, Guan, Liu, Wenjie, Lin, Jiajie, Su, Zepeng, Che, Yunshu, Ye, Feng, Ma, Mengjun, Xie, Zhongyu, Shen, Huiyong |
| المساهمون: | National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Science and Technology Project of Shenzhen City, Public Health and Welfare Research Project of Futian District of Shenzhen, Natural Science Foundation of Guangdong Province |
| المصدر: | Human Molecular Genetics ; volume 30, issue 3-4, page 277-293 ; ISSN 0964-6906 1460-2083 |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2020 |
| الوصف: | Ankylosing spondylitis (AS) is a rheumatic disease with pathological osteogenesis that causes bony ankylosis and even deformity over time. Mesenchymal stem cells (MSCs) are multipotent stem cells that are the main source of osteoblasts. We previously demonstrated that enhanced osteogenic differentiation of MSCs from AS patients (ASMSCs) is related to pathological osteogenesis in AS. However, the more concrete mechanism needs further exploration. Super enhancers (SEs) are dense clusters of stitched enhancers that control cell identity determination and disease development. Single-nucleotide polymorphisms (SNPs) regulate the formation and interaction of SEs and denote genes accounting for AS susceptibility. Via integrative analysis of multiomic data, including histone 3 lysine 27 acetylation (H3K27ac), chromatin immunoprecipitation sequencing (ChIP-seq), SNPs and RNA sequencing (RNA-seq) data, we discovered a transcription network mediated by AS SNP-adjacent SEs (SASEs) in ASMSCs and identified key genes, such as Toll-like receptor 4 (TLR4), interleukin 18 receptor 1 (IL18R1), insulin-like growth factor binding protein 4 (IGFBP4), transportin 1 (TNPO1) and proprotein convertase subtilisin/kexin type 5 (PCSK5), which are pivotal in osteogenesis and AS pathogenesis. The SASE-regulated network modulates the enhanced osteogenic differentiation of ASMSCs by synergistically activating the PI3K-Akt, NF-kappaB and Hippo signaling pathways. Our results emphasize the crucial role of the SASE-regulated network in pathological osteogenesis in AS, and the preferential inhibition of ASMSC osteogenic differentiation by JQ1 indicates that SEs may be attractive targets in future treatment for new bone formation in AS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1093/hmg/ddaa272 |
| DOI: | 10.1093/hmg/ddaa272/36232049/ddaa272.pdf |
| الاتاحة: | https://doi.org/10.1093/hmg/ddaa272 http://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddaa272/36232049/ddaa272.pdf http://academic.oup.com/hmg/article-pdf/30/3-4/277/37771924/ddaa272.pdf |
| Rights: | https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model |
| رقم الانضمام: | edsbas.990C61CD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/hmg/ddaa272 |
|---|