Affiliation:
1. Shenzhen Futian Hospital for Rheumatic Diseases, China
2. Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional and Western Medicine, China
3. Rheumatism Dept. Yunnan Provincial Hospital of Traditional Chinese Medicine, China
Abstract
Objectives. Synovial fibroblasts (SFs) play an important role in the development and progression of rheumatoid arthritis (RA). However, the pathogenic mechanism of SFs remains unclear. The objective of this study was to investigate how neuropeptides and N6-methyladenosine (m6A) played an important role in the underlying pathogenic processes of SFs that contribute to the development of RA. Methods. Single-cell RNA sequencing data were examined using single-cell analysis and machine learning. SF subgroups were identified based on the clustering and annotation results of the single-cell analysis. Moreover, cell–cell communication was used to analyse neuropeptide-related receptor and ligand pairs on the surface of SF cell membranes. Machine learning was used to explore the m6A factors acting on these neuropeptide genes. Results. NPR3, GHR, BDKRB2, and CALCRL, four neuropeptide genes, were shown to be differently expressed among SF subgroups. Further investigation of receptor–ligand interactions found that NPR3 (in conjunction with NPPC, OSTN, NPPB, and NPPA) and GHR (in conjunction with GH1 and GH2) may have a role in SF interactions. As predicted by machine learning, IGFBP2 and METTL3 were identified as key factors regulating m6A of NPR3 and GHR. The expression levels and enrichment pathways of METTL3 and IGFBP2 were different among SF subgroups. Conclusions. Single-cell analysis and machine learning efficiently identified neuropeptide genes and m6A factors that perform important regulatory functions in RA. Our strategy may provide a basis for future studies to identify pathogenic cell subpopulations and molecular mechanisms in RA and other diseases.
Funder
Chinese Medicine Research Project of Traditional Chinese Medicine Bureau of Guangdong Province
Subject
Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine
Cited by
14 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献