Synovial hyperplasia, inflammation and immune cell infiltration are the central pathological basis of rheumatoid arthritis (RA). Nonetheless, the cellular, molecular and immunological mechanisms of RA remain poorly understood. An integrated analysis of single-cell RNA (scRNA) and bulk RNA sequencing datasets aimed to unravel the cellular landscape, differentiation trajectory, transcriptome signature, and immunoinfiltration feature of RA synovium. Multilevel experiments were conducted to investigate the role and mechanism of MEG3 in the aggravation and reversal of RA. We screened 97 intergroup differential genes of single-cell transcriptome profiles in the RA versus PsA comparison, which were principally associated with metabolism, inflammation, and proliferation. Clustering and annotation analysis defined 7 key cell subpopulations (monocytes, epithelial cells, CD8