Decoding Dental Mesenchymal Stem Cells Diversity: Single-Cell Transcriptomics Maps Heterogeneity in Molar Development

Ruilin ZhangLeyi ChenWanli XuXu Wen-anBuling Wu^*

• Southern Medical University, Guangzhou, China

ABSTRACT The spatial and temporal differences influence the development of vertebrate teeth in specific cell types, as well as the precise regulation of signalling networks. During early embryogenesis, the odontogenic potential shifts from the dental epithelium to the mesenchyme, initiating subsequent morphogenetic processes. Across the bud, cap, and bell stages, incisors and molars undergo distinct morphological and functional transformations driven by dynamic mesenchymal subpopulations. These subpopulations exhibit temporally specific gene expression profiles and differentiation trajectories, which orchestrate crown-root patterning, odontoblast differentiation, and pulp-stroma interactions. Recent advances in single-cell RNA sequencing (scRNA-seq) have revolutionised our understanding of dental mesenchymal heterogeneity, unveiling previously unidentified progenitor populations and their regulatory networks. By mapping developmental trajectories and intercellular communication, scRNA-seq has elucidated the transition of mesenchymal cells between stat dental papilla precursors, follicle progenitors, and apical papilla stem cells. Furthermore, this technology highlights the functional divergence of mesenchymal stem cells (MSCs) in postnatal teeth, which balance mineralisation, immune modulation, and repair capacities. However, in vitro expansion of MSCs alters their native properties, underscoring the importance of niche-specific signaling. This review synthesises scRNA-seq findings to review the hierarchy of dental mesenchymal subpopulations, offering insights into their roles in developmental defects and regenerative strategies. These discoveries bridge developmental biology and clinical applications, paving the way for novel therapies in tooth regeneration and pulp repair.