ABSTRACT Objective To investigate the distribution, lineage fate, and reparative function of Thy1 lineage cells in the mouse mandible. Methods Single‐cell transcriptomic analysis was used to identify osteogenic subpopulations within mandibular mesenchymal stem cells. Lineage tracing in Thy1‐CreERT2;Rosa26‐tdTomato mice was employed to map the localization and osteogenic contribution of Thy1 lineage cells, while a critical‐sized mandibular defect model was established to assess their reparative dynamics. Loss‐ and gain‐of‐function experiments were performed using Thy1‐CreERT2;Rosa26‐DTR mice and transplantation of purified tdTomato + periosteal cells within hydrogel scaffolds. Results Single‐cell analysis identified a Thy1‐enriched osteoprogenitor subpopulation preferentially localized to the periosteum. Lineage tracing revealed that Thy1‐lineage cells constituted a major proportion of periosteal osteogenic cells and exhibited clonogenic expansion and ectopic bone formation. Following mandibular injury, tdTomato + cells progressively accumulated within the callus and represented the predominant osteogenic cell population at later stages. Genetic ablation of Thy1‐lineage cells markedly impaired bone repair, whereas transplantation of purified tdTomato + periosteal cells enhanced bone formation within the defect. Conclusions Thy1 lineage periosteal cells represent a functionally important osteoprogenitor population in mandibular bone regeneration, providing a cellular framework for future mechanistic and translational studies.
Zhang et al. (Wed,) studied this question.