Mx1-labeled pulp progenitor cells are the main contributors of odontoblast and dentin regeneration in murine molars.

Regeneration of dentin and odontoblasts from dental pulp progenitor cells is essential for the maintenance of permanent tooth. However, the in vivo identity of endogenous pulp progenitor cells and how they contribute to reparative dentinogenesis remain elusive. Here we show that comparative single-cell analysis of pulp cells before and after molar eruption reveal that endogenous pulp progenitor cells are enriched in coronal papilla-like cells with Mx1-Cre and Cxcl12-GFP expression. Further, lineage tracing and fluorescence-activated cell sorting analysis indicated that Mx1-labeled (Mx1(+)) pulp cells include long-term repopulating progenitor cells with higher expression of stem cell markers. Notably, these Mx1(+) progenitor cells contribute to the majority of pulp cells and new odontoblast-like cells in the loaded plane of the molar after eruption. Upon molar injury, Mx1(+) progenitor cells localize into the injury site and differentiate into new odontoblast-like cells, forming osteocalcin-GFP(+) and scleraxis-GFP(+) processes to reoccupy existing dentinal tubules and reparative dentin formation. Taken together, our findings demonstrate that Mx1 labels dental pulp progenitor cells, which are the major source of pulp cells and odontoblast-like cells with reparative dentinogenesis in vivo.