Single-cell transcriptional profiling reveals PAX5-mediated naïve B cell differentiation defect in severe adenoid hypertrophy.
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BACKGROUND: Adenoid hypertrophy significantly impacts pediatric upper airway function, but its molecular mechanisms remain elusive. This study characterizes the cellular landscape in adenoid hypertrophy using single-cell RNA sequencing (scRNA-seq). METHODS: Adenoid tissue samples were obtained from pediatric patients diagnosed with either severe hypertrophic adenoids (SHA) and mild to moderate hypertrophic adenoids (MHA). scRNA-seq was performed to generate transcriptomic profiles at single-cell resolution. Clustering and differential expression analyses were performed, with pseudotime trajectory, cell-cell communication, and copy number variation analyses. RESULTS: Analysis of 45,917 single-cell transcriptomes revealed 18 distinct cell clusters with B cells predominating. SHA samples exhibited significant enrichment of naïve B cells with corresponding reduction of memory B cells, suggesting disrupted B cell differentiation. Pseudotime analysis confirmed B cell differentiation disruption in SHA, with cells accumulating at the naïve B cell stage. Notably, paired box gene 5 (PAX5), a master transcription factor essential for B cell lineage commitment but typically downregulated during terminal differentiation, was significantly upregulated in SHA. CNV analysis showed no evidence of clonal expansion or malignant transformation. CONCLUSIONS: Our findings reveal that adenoid hypertrophy is characterized by impaired B cell differentiation with accumulation of naïve B cells and PAX5 overexpression, suggesting a differentiation blockade as a novel pathogenic mechanism. These insights offer potential therapeutic targets within the B cell maturation pathway, including modulation of PAX5 activity.