Single-cell characterization of human periodontal ligament (PDL) cells reveals uniformly mesenchymal populations in matched maxilla and mandible pairs from four donors

Single-cell RNA sequencing was employed to analyze cultured primary periodontal ligament (PDL) cells derived from matched upper (maxilla) and lower (mandible) jaw sites of four donors. The study revealed that these expanded cultures are uniformly mesenchymal and fibroblastic, with minimal endothelial and immune signatures. Rather than forming discrete cell types, the cells clustered into ten distinct fibroblast substates, including proliferating, collagen- and extracellular-matrix-high, contractile, and progenitor-like populations.

Donor identity emerged as the primary factor influencing the transcriptional profiles of these cells, with several substates restricted to individual donors. When comparing maxilla and mandible tissues, only a limited set of differentially expressed genes were identified, primarily involving craniofacial positional-identity transcription factors (PITX1 in the mandible and BARX1, ALX1, and NKX6-1 in the maxilla). This suggests that cultured PDL cells maintain their embryonic positional memory.

Interestingly, the study did not find significant differences in curated wound-healing gene modules between the maxilla and mandible, challenging the clinical assumption of faster healing in the maxilla. Instead, the transcriptional data implies that the healing asymmetry may be due to vascular, mechanical, and inflammatory signaling factors acting outside of the steady-state transcriptome.

Overall, this research characterizes the cellular composition of expanded PDL cultures and highlights positional identity as the main jaw-dependent transcriptional feature.