Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease.

Ana J Caetano,Eleanor M D'Agostino,Paul Sharpe,Ana Volponi,Val Yianni,Veronica Booth

doi:10.7554/elife.62810

Ana J Caetano, Eleanor M D'Agostino + Show 4 more

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https://doi.org/10.7554/elife.62810

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Abstract

Human oral soft tissues provide the first barrier of defence against chronic inflammatory disease and hold a remarkable scarless wounding phenotype. Tissue homeostasis requires coordinated actions of epithelial, mesenchymal, and immune cells. However, the extent of heterogeneity within the human oral mucosa and how tissue cell types are affected during the course of disease progression is unknown. Using single-cell transcriptome profiling we reveal a striking remodelling of the epithelial and mesenchymal niches with a decrease in functional populations that are linked to the aetiology of the disease. Analysis of ligand-receptor interaction pairs identify potential intercellular hubs driving the inflammatory component of the disease. Our work establishes a reference map of the human oral mucosa in health and disease, and a framework for the development of new therapeutic strategies.

Highlights

The oral mucosa is one of the most rapidly dividing tissues in the body and provides the first line of defence against the development of oral disease
To provide an in-depth analysis of cellular architecture, cell heterogeneity, and understand gingival cell dynamics when transitioning from health to disease, we transcriptionally profiled single cells derived from patients
We identified a marked decreased in the myofibroblast (S1) and pericyte (S3) subpopulations in the mild stage, while the other fibroblast-like cells appeared unchanged with the exception of S6 (Figure 2B)

Summary

Introduction

The oral mucosa is one of the most rapidly dividing tissues in the body and provides the first line of defence against the development of oral disease. Periodontal disease is a chronic inflammatory condition associated with a dysbiosis of the commensal oral microbiota and host immune defences causing irreversible destruction of the soft and hard supporting tissues of the teeth (Pihlstrom et al, 2005; Lindhe et al, 2008). Chronic periodontitis occurs when untreated gingivitis progresses to the loss of the gingiva, bone, and ligament (Lamont and Hajishengallis, 2015; Pihlstrom et al, 2005; Lindhe et al, 2008). Regenerating lost tissues remains the fundamental therapeutic goal and to achieve this it is necessary to understand the mechanisms and pathways controlling disease progression while identifying novel candidates for intervention

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