Decoding SFRP2hi Fibroblast Progenitors in Sustaining Tooth Growth in Humans and Mice at Single-Cell Resolution

Single-cell transcriptomics has revolutionized tooth biology by uncovering previously unexplored areas. The mouse is a widely used model for studying human tissues and diseases, including dental pulp tissues. While human and mouse molars share many similarities, mouse incisors differ significantly from human teeth due to their continuous growth throughout their lifespan. The extent to which studies on mouse teeth can be applied to human disease translation remains underexplored. By leveraging multiple single-cell datasets, we constructed a comprehensive dental pulp cell landscape to clarify tissue similarities and species-specific differences between humans and mice. Notably, we identified a distinct cell population, Sfrp2hi fibroblast progenitors, found exclusively in mouse incisors and the developing tooth root of human molars. These cells are uniquely present to sustain continuous tissue growth. Mechanistically, we found that the transcription factor Twist1, regulated by MAPK phosphorylation, binds to the Sfrp2 promoter and modulates Wnt signaling activation to maintain stem cell identities. Our research reveals a previously unrecognized subset of dental mesenchymal stem cells instrumental in tooth growth. This distinct subset is evolutionarily conserved in both humans and mice, offering valuable translational insights. Overall design: Mouse incisors from mandibles were carefully dissected from 15 C57BL/6 mice aged 7 weeks. The incisor pulp, with minimal inclusion of dental epithelium, was isolated and analysed using scRNAseq.