Integrated single-cell RNA sequencing analysis reveals phenotypic differences between blood endothelial cells from...

The oral mucosa and the skin are two barrier tissues acting as the first line of defense protecting our body from external forces and invaders. Although these tissues are histologically quite similar, differences have been described related to their epidermal and immunological functions. However, very little is known about differences which may exist between oral mucosa and skin vasculature. The aim of this study was to characterize phenotypic differences between blood endothelial cells (BECs) from oral mucosa and skin.

Three publicly available single-cell RNA sequencing (sc-RNA seq) datasets from gingiva, buccal mucosa and skin were integrated. Differential gene expression between BECs of the different tissues was analyzed. Upregulated genes were used to perform pathway enrichment analysis. Tissue sections derived from healthy gingiva, buccal mucosa and skin biopsies were used to validate sc-RNA seq findings.

Differential gene expression and pathway enrichment analysis revealed a more angiogenic and dynamically remodeling endothelial phenotype in gingival and buccal mucosa BECs compared to skin BECs. Among the most differentially expressed genes upregulated in oral BECs compared to skin were SOX18 and HEG1, while FABP4 and ANGPT2 were upregulated in skin BECs. This gene expression pattern was validated on healthy native biopsies obtained from skin, gingiva and buccal mucosa.

These findings identify distinct endothelial cell phenotypes of oral and skin blood vasculature, highlighting the ability of endothelial cells to adapt to the oral and skin microenvironment.