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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease

ABSTRACT: Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease

PROVIDER: PRJNA851592 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19777662_1.fastq.gz	Fastqsanger.gz
	SRR19777662_2.fastq.gz	Fastqsanger.gz
	SRR19777663_1.fastq.gz	Fastqsanger.gz
	SRR19777663_2.fastq.gz	Fastqsanger.gz
	SRR19777664_1.fastq.gz	Fastqsanger.gz

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Mapping the Spatial Dynamics of the Human Oral Mucosa in Chronic Inflammatory Disease

Project description: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 define highly specialised epithelial and stromal compartments and describe location-specific immune programs. Furthermore, we discovered fine regional fibroblast states, and spatially mapped a rare pathogenic 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.

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Project description:Injuries of the vocal folds frequently heal with scar formation, which can have lifelong detrimental impact on voice quality. Current treatments to prevent or resolve scars of the vocal fold mucosa are highly unsatisfactory. In contrast, the adjacent oral mucosa is mostly resistant to scarring. These differences in healing tendency might relate to distinct properties of the fibroblasts populating oral and vocal fold mucosae. We thus established the in vitro cultivation of paired, near-primary vocal fold fibroblasts (VFF) and oral mucosa fibroblasts (OMF) to perform a basic cellular characterization and comparative cellular proteomics. VFF were significantly larger than OMF, proliferated more slowly, and exhibited a sustained TGF-β1-induced elevation of pro-fibrotic interleukin 6. Cluster analysis of the proteomic data revealed distinct protein repertoires specific for VFF and OMF. Further, VFF displayed a broader protein spectrum, particularly a more sophisticated array of factors constituting and modifying the extracellular matrix. Conversely, subsets of OMF-enriched proteins were linked to cellular proliferation, nuclear events, and protection against oxidative stress. Altogether, this study supports the notion that fibroblasts sensitively adapt to the functional peculiarities of their respective anatomical location and presents several molecular targets for further investigation in the context of vocal fold wound healing.

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