Decoding regional keratinization in human oral mucosa through high-resolution spatial transcriptomics

Area of Science:

• Oral biology
• Histology
• Regenerative medicine

Background:

• Oral mucosa keratinization is vital for periodontal health but its mechanisms are unclear.
• Region-specific differences in oral mucosa keratinization require further investigation.

Purpose of the Study:

• To create a high-resolution spatial transcriptomic atlas of the human oral mucosa near the mucogingival junction.
• To identify stromal-epithelial interactions that differentiate keratinized and non-keratinized oral mucosa programs.

Main Methods:

• Analysis of formalin-fixed paraffin-embedded oral mucosa specimens using the 10x Genomics Visium HD platform.
• Application of spatial clustering, pseudotime trajectory inference, cell-type integration, and ligand-receptor network analysis.
• Identification of distinct transcriptional signatures in keratinized (gingiva) and non-keratinized (lining mucosa) regions.

Main Results:

• Generated a spatial transcriptomic atlas revealing 16 reproducible clusters mirroring tissue architecture.
• Identified bifurcating epithelial lineages from basal progenitors into keratinized and non-keratinized programs.
• Discovered that stromal collagen ligands (COL1A1, COL1A2, COL6A1, COL6A2) binding epithelial receptors (CD44, SDC1) drive gingival keratinization, reinforced by desmosomal adhesion (DSG1-DSC2/3).

Conclusions:

• Gingival keratinization results from integrated stromal collagen signaling and epithelial adhesion.
• This study provides a spatially resolved framework for understanding oral mucosal specialization.
• The findings lay the groundwork for developing targeted regenerative therapies for oral mucosal conditions.