Single-cell transcriptional profiling reveals cellular senescence and inflammatory persistence as key features of type 1 diabetes partial remission.

Abstract

Aims: To investigate the underlying immune mechanisms during partial remission (PR) in type 1 diabetes (T1D) using single-cell RNA sequencing of peripheral blood mononuclear cells from healthy controls, newly diagnosed T1D patients, and those in the PR stage.

Materials and methods: We performed integrated analysis combining differential expression analysis, trajectory inference, cellular senescence evaluation and transcriptional network reconstruction to characterize monocyte heterogeneity and dynamic changes during disease progression. We identified five distinct monocyte subsets with unique molecular signatures and demonstrated their stage-specific alterations.

Results: The PR stage was characterized by persistent inflammatory responses, evidenced by the expansion of IL1B+ monocytes and sustained activation of TNF and IL6-STAT3 signalling pathways, while HDAC9+ populations showed significant reduction. Notably, the PR stage exhibited marked accumulation of senescent cells across monocyte subsets, demonstrated by elevated senescence-associated secretory phenotype scores and increased P21 expression. Trajectory analysis revealed altered developmental dynamics during PR, with distinct classical and non-classical monocyte branches. Transcriptional network analysis identified sustained activation of EGR1 and NFκB signalling throughout disease progression, particularly during PR.

Conclusion: These findings reveal previously unrecognized features of immune dysregulation during PR and provide potential therapeutic targets for T1D treatment.