Plap-1 lineage tracing and single-cell transcriptomics reveal cellular dynamics in the periodontal ligament.

Periodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated protein-1 (Plap-1) as a PDL-specific extracellular matrix protein. We generated knock-in mice expressing CreERT2 and GFP specifically in Plap-1-positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiate into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1-Ibsp+Sparcl1+ and Plap-1-Ibsp+Col11a2+, respectively. Other populations, such as Nes+ mural cells, S100B+ Schwann cells, and other non-stromal cells, were also identified. RNA velocity analysis suggested that a Plap-1highLy6a+ cell population was the source of PDLCs. Lineage tracing of Plap-1+ PDLCs during periodontal injury showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.

Asymmetric requirement of surface epithelial ß-catenin during the upper and lower jaw development.

BACKGROUND: Intercellular communication between epithelial and mesenchymal cells is central to mammalian craniofacial development. ß-catenin is the gateway of canonical Wnt signaling, one of the major evolutionarily conserved cell-cell communication pathways in metazoa. In this study, we report an unexpected stage- and tissue-specific function of ß-catenin during mammalian jaw development. RESULTS: Using a unique mouse genetic tool, we have discovered that epithelial ß-catenin is essential for lower jaw formation, while attenuation of ß-catenin is required for proper upper jaw development. Changes in ß-catenin in vivo alter major epithelial Fgf8, Bmp4, Shh, and Edn1 signals, resulting in partial transcriptional reprogramming of the neural crest-derived mesenchyme, the primary source of jawbones. CONCLUSIONS: The Wnt/ß-catenin signal coordinates expression of multiple epithelial signals and has stage-specific asymmetric functions during mammalian upper and lower jaw development. In addition, these findings suggest that evolutionary changes of the canonical Wnt/ß-catenin signaling pathway may lead to innovation of jaws.