Artificial intelligence-guided single-cell transcriptomic analysis for identifying O-GlcNAc transferase in fibroblast-like synoviocytes as a therapeutic target for rheumatoid arthritis

ABSTRACT: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation, synovial hyperplasia, and the destruction of bone and cartilage. Despite the use of various immunosuppressive disease-modifying antirheumatic drugs (DMARDs), a considerable proportion of RA patients remain symptomatic. As RA progresses, fibroblast-like synoviocytes (FLSs) undergo a phenotypic transition to an aggressive state, making them attractive non-immune cellular targets for RA treatment. However, there are currently no clinically available therapies that selectively ablate RA-FLSs due to the lack of specific molecular targets. Our research focuses on the knockdown of the OGT and SAP130 genes in RA-FLSs. OGT and SAP130 are expressed in the cell of RA-FLSs and plays a crucial role in their aggressive transition. By specific knockout of OGT and SAP130 we observed a significant supression of aggressive transformations of RA-FLS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE315144 | GEO | 2026/09/01

REPOSITORIES: GEO