Unveiling the dental cellular landscape: A comprehensive review of single-cell RNA sequencing in human dental tissues

Single-cell RNA sequencing (scRNA-seq) has advanced the understanding of cellular heterogeneity and molecular dynamics in human dental tissues. This systematic review critically evaluated scRNA-seq studies exploring the cellular composition of human dental tissues, comparing in situ and cultured environments under both healthy and diseased conditions. Original research articles meeting the inclusion criteria were assessed for cell type identification, transcriptional profiles, analytical platforms, and other key biological insights by two independent authors. A total of fifteen studies that met the inclusion criteria revealed diverse cell populations, including mesenchymal stem cells (MSCs), immune cells, endothelial cells, and odontoblast-like cells, each exhibiting distinct transcriptional signatures in homeostasis, regeneration, and disease. Key findings included distinct MSC subpopulations, including THY1+, CD24+, FRZB+, and NOTCH3+/PDGFRB+, exhibiting unique differentiation potential, along with significant heterogeneity in odontoblast lineage. Moreover, carious dental pulp undergoes a fibrotic transcriptional shift (e.g., COL1A1, FN1, and TNC), whereas periodontitis exhibits increased expression of pro-inflammatory cytokines (IL-1β and TNFα) and diminished periodontal MSC regenerative capacity. This review underscores the contributions of scRNA-seq in providing unprecedented insights into the complexity and functional heterogeneity of dental tissues, offering a foundation for advancing targeted regenerative therapies and guiding future translational research in dental medicine.