Biology subjects

Sharpe, P.

Publications and source records attributed to Sharpe, P..

4 recordsLinked to original sources

bioRxiv2025

Characterising the periodontal granulation tissue using scRNAseq.

AimsOur research investigated the cellular composition and molecular mechanisms of periodontal granulation tissue using single-cell RNA sequencing (scRNA-seq), aiming to enhance the understanding of periodontal disease pathogenesis and identify potential targets for regenerative therapies. Materials and MethodsGranulation tissue samples were collected from patients undergoing periodontal surgery. Fresh tissues were processed into single-cell suspensions and subjected to scRNA-seq. The data were integrated with existing datasets from healthy gingiva and periodontal ligament. Computational analyses were performed, and validation through immunofluorescence staining. ResultsTen distinct cell clusters were identified across the samples. Granulation tissue exhibited a higher abundance of immune cells compared to healthy tissues. A novel endothelial cell subpopulation, exclusive to granulation tissue, was discovered, characterized by NOTCH3 expression and involvement in ossification pathways. Additionally, granulation tissue Fibroblast subpopulations demonstrated a progenitor-like state, characterized by extracellular matrix reorganization and low differentiation, similar to cancer-associated fibroblasts. Conclusion(s)This study advances the understanding of periodontal disease by characterizing key regulatory cell populations within granulation tissue. The identification of the novel endothelial subpopulation offers new insights into the diseases pathogenesis and presents potential targets for regenerative therapies. These findings suggest opportunities for developing biomaterials that modulate specific cellular pathways to improve periodontal disease treatment.

cell biology↗

bioRxiv2022

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

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.

cell biology↗

bioRxiv2021

Telocytes regulate macrophages in periodontal disease

BackgroundTelocytes (TCs) or interstitial cells are characterised in vivo by their long projections that contact other cell types. Although telocytes can be found in many different tissues in luding the heart1, lung2 and intestine3, their tissue-specific roles are poorly understood. Here we identify a cell signalling role for telocytes in the periodontium whereby telocytes regulate macrophage activity. MethodsWe performed scRNA-seq and lineage tracing to identify TCs in mouse periodontium in homeostasis and periodontitis and carried out HGF signalling inhibition experiments using Tivantinib. ResultsWe demonstrated that TCs are quiescent in homeostasis, however, they proliferate and serve as a major source of HGF in periodontitis. Macrophages receive telocyte-derived HGF signals and shift from an M1 to a M1/M2 hybrid state. ConclusionsOur results reveal the source of HGF signals in periodontal tissue and provide new insights into the function of TCs in regulating macrophage behaviour in periodontitis through HGF/c-Met cell signalling, that may provide a novel approach in periodontitis treatment. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/446871v2_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@12e0491org.highwire.dtl.DTLVardef@2de4d0org.highwire.dtl.DTLVardef@10936a8org.highwire.dtl.DTLVardef@1e36089_HPS_FORMAT_FIGEXP M_FIG A population of telocytes (TC) have been identified in the periodontium. They are quiescent in homeostasis, however, in periodontitis, they are activated and send HGF signals to LPS activated iNOS+ (M1) macrophages. Macrophages receive the HGF signals via c-Met, which results in the expression of M2 marker Arg1, representing in an increase of M1/M2 hybrid macrophages. The expression of Arg1 can be inhibited by a HGF/c-Met selective inhibitor Tivantinib. C_FIG

cell biology↗

bioRxiv2020

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

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.

cell biology↗