RT Journal Article SR Electronic T1 Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.07.05.498778 DO 10.1101/2022.07.05.498778 A1 Ana J. Caetano A1 Yushi Redhead A1 Farah Karim A1 Pawan Dhami A1 Shichina Kannambath A1 Rosamond Nuamah A1 Ana A. Volponi A1 Luigi Nibali A1 Veronica Booth A1 Eleanor M. D’Agostino A1 Paul T. Sharpe YR 2022 UL http://biorxiv.org/content/early/2022/07/05/2022.07.05.498778.abstract AB The interplay among different cells in a tissue is essential for maintaining homeostasis. Although, disease states have been traditionally attributed to individual cell types, increasing evidence and new therapeutic options have demonstrated the primary role of multicellular functions to understand health and disease, opening new avenues to understand pathogenesis and develop new treatment strategies. We recently described the cellular composition and dynamics of the human oral mucosa; however, the spatial arrangement of cells is needed to better understand a morphologically complex tissue. Here, we link single-cell RNA sequencing, spatial transcriptomics, and high-resolution multiplex fluorescence in situ hybridisation to characterise human oral mucosa in health and oral chronic inflammatory disease. We deconvolved expression for resolution enhancement of spatial transcriptomic data and defined highly specialised epithelial and stromal compartments describing location-specific immune programs. Furthermore, we spatially mapped a rare pathogenic fibroblast population localised in a highly immunogenic region, responsible for lymphocyte recruitment through CXCL8 and CXCL10 and with a possible role in pathological angiogenesis through ALOX5AP. Collectively, our study provides a comprehensive reference for the study of oral chronic disease pathogenesis.Competing Interest StatementThe authors have declared that no conflict of interest exists. However, E. DA is an employee of Unilever Plc.