Research progress in heterogeneity of dental mesenchymal stem cells

Dental tissues development involves two distinct cell lineages: mesenchymal cells (derived from the cranial neural crest) and epithelial cells (derived from oral ectoderm and pharyngeal epithelium). Emerging evidence highlights the remarkable functional heterogeneity of cranial neural crest-derived dental mesenchymal stem cells (DMSCs), exhibiting pluripotency, self-renewal, and differentiation capacities. This heterogeneity enables a single DMSC population to generate specialized subpopulations with unique roles in teeth and periodontal tissues formation. Significant progress has been made in characterizing six major types of DMSCs and two populations of closely related cells: Tooth germ progenitor cells (TGPCs) and dental follicle stem cells (DFSCs), critical during early morphogenesis; Stem cells from human exfoliated deciduous teeth (SHEDs) and apical papilla stem cells (SCAPs), pivotal for root development; Dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), gingival mesenchymal stem cells (GMSCs) and alveolar bone mesenchymal stem cells (ABMSCs), essential for maintaining and regenerating mature dental tissues. A key breakthrough has unveiled the development and hierarchy of DMSCs by applying new techniques like single-cell RNA sequencing (scRNA-seq). To integrate insights into the development of teeth and periodontal tissues, this review synthesizes current knowledge on both developmental heterogeneity and subpopulation heterogeneity within DMSCs and related cells. These insights not only advance fundamental understanding of the developmental mechanisms of teeth and periodontal tissues, but also establish a promising framework for achieving more efficient tissue regeneration and repair engineering.