Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveal macrophage subpopulation characteristics and the role of STAT1 in rheumatoid arthritis.

backgroundRheumatoid arthritis (RA) represents a persistent systemic autoimmune disorder characterized by chronic inflammation and significant disability. Macrophage heterogeneity plays a crucial role in the progression of RA, but the molecular characteristics and regulatory mechanisms of its subsets have not yet been fully elucidated.

methodsIn this study, we integrated single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (bulk RNA-seq) data, and employed multiple strategies for analysis and identification of the heterogeneity of macrophages in RA. We identified STAT1 as a key gene through a combined approach utilizing LASSO regression and random forest models. The differential expression of STAT1 was subsequently validated in an adjuvant-induced arthritis (AIA) rat model. Furthermore, functional experiments were performed to investigate the association of STAT1 with autophagy and ferroptosis pathways.

resultsBased on scRNA-seq data, a total of 26,923 cells were subjected to multi-dimensional analysis. The synovial tissues of RA mice exhibited a markedly elevated percentage of macrophages expressing Stat1. Enrichment analysis indicated that Stat1

conclusionsThis study elucidated the heterogeneity and functional characteristics of macrophage subsets in RA synovial tissue through scRNA-seq and bulk RNA sequencing, and suggested that STAT1 and its downstream signaling pathways may serve as potential therapeutic targets for RA.