Single-cell sequencing unveils the heterogeneity of nonimmune cells in chronic apical periodontitis

Chronic apical periodontitis (CAP) is a unique dynamic interaction between microbial invasions and host defense mechanisms, resulting in bone absorption, infiltration of immune cells and sporadic periapical granuloma. In this study, we constituted a single-cell atlas for 26,737 high-quality cells from hyperplastic periapical tissue using single-cell RNA sequencing. Identifying cell types and signatures at the single-cell level might generate novel insights into the clinical pathogenesis of CAP. A histological analysis to verify the gene signatures of nonimmune cells was combined with immunohistochemistry staining. We then discovered the diversity and heterogeneity of nonimmune cells in regional CAP lesions. The temporal profiling of genomic alterations from common CAP to typical periapical granuloma provided predictions for key transcription factors and biological processes. Our study also inferred that the marked shift of inflammatory cytokines, chemokines, proteases and growth factors enables the initiation of polymorphic cell differentiation, lymphangiogenesis and angiogenesis during CAP. Overall design: Three samples from extracted residual molars with chronic apical periodontitis