Mx1-labeled pulp progenitor cells are main contributors to postnatal odontoblasts and pulp cells in murine molars

Regeneration of dentin and odontoblasts from dental pulp stem cells (DPSCs) is essential for permanent tooth maintenance. However, the in vivo identity and role of endogenous DPSCs in reparative dentinogenesis are elusive. Here, using pulp single-cell analysis before and after molar eruption, we revealed that endogenous DPSCs are enriched in Cxcl12-GFP+ coronal papilla-like cells with Mx1-Cre labeling. These Mx1+Cxcl12-GFP+ cells are long-term repopulating cells that contribute to the majority of pulp cells and new odontoblasts after eruption. Upon molar injury, Mx1+ DPSCs localize into the injury site and differentiate into new odontoblasts, forming scleraxis-GFP+ and osteocalcin-GFP+ dentinal tubules and reparative dentin. Single-cell and FACS analysis showed that Mx1+Cxcl12-GFP+ DPSCs are the most primitive cells with stem cell marker expression and odontoblast differentiation. Taken together, our findings demonstrate that Mx1 labels postnatal DSPCs, which are the main source of pulp cells and new odontoblasts with reparative dentinogenesis in vivo.