ScRNA-seq Analysis of Olfactory Epithelium in Chronic Rhinosinusitis with Nasal Polyps 2261022

Abstract Introduction Olfactory epithelium inflection is associated with olfactory dysfunction, but the specific target cells and regulatory mechanisms in chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. Methods To explore cellular and molecular mechanism underlying olfactory dysfunction in CRSwNP, we performed single-cell RNA sequencing (scRNA-seq) on superior turbinate tissues from 4 control subjects and 3 CRSwNP patients following endoscopic sinus surgery. Results We profiled 32,367 cells and distinguished key epithelial cell types, including olfactory epithelium cells (sustentacular, Bowman’s glands, horizontal basal cells, microvillar, and olfactory sensory neuron-like cells) and respiratory epithelium cells (ciliated, seromucous glandular, goblet, ionocytes, and tuft cells). Immune cells such as B cell, T cell, NK, myeloid, mast cells were also identified. Lipocalin 15 (LCN15) and other target proteins were significantly decreased in CRSwNP and may be associated with olfaction dysfunction. GSEA indicated revealed distinct signaling pathway enriched in CRSwNP, suggest disease-specific molecular dysregulating affecting olfactory function. Conclusion scRNA-seq of CRSwNP tissues reveals diverse epithelial populations and highlights altered pathways potentially driving olfactory dysfunction. These findings offer new insight into disease mechanisms and may inform future therapeutic strategies. Funding Source R01 AI134952, R01 DC016645, P01 AI145818 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)