Identification of Periosteal Osteogenic Progenitors in Jawbone

Objectives: Unlike long bones, jawbone development is mainly accomplished by intramembranous ossification resulting from the differentiation of periosteal progenitor cells. However, the spatiotemporal ontogeny of periosteal progenitor cells during jawbone development and repair remains elusive. Thus we attempted to identify periosteal specific progenitors.
Methods: In this study, we mapped the transcriptional landscape of the human jawbone periosteum at single-cell resolution to identify jawbone periosteal specific markers, combining with lineage tracing mice we identified a osteogenic cluster of periosteal specific progenitors.
Results: With the help of scRNA-seq, we identified a cathepsin K (Ctsk)⁺ periosteal subset. Lineage tracing analysis indicated that Ctsk-Cre-labeled periosteal cells could make contributions to jawbone development. However, different from the periosteal specific location of Ctsk⁺ cells in long bone, we also identified Ctsk⁺ stromal cells in jawbone marrow, implied the heterogeneity of jawbone Ctsk⁺ hierarchy. In further analysis of the periosteal progenitor cells subset of heterogeneous Ctsk⁺ hierarchy, we identified a unique Ctsk⁺Ly6a⁺ subset of cells. The additional marker Ly6a helped to further confined the progenitor subset to the jawbone periosteum and were nearly undetectable in the bone marrow. Defects in the jawbone could activate the osteogenic differentiation of Ctsk⁺Ly6a⁺ cells. Local ablation of Ctsk⁺ cells by diphtheria reduced the number of Ctsk⁺Ly6a⁺ cells and delayed the repair of the bone defect.
Conclusions: Taken together, we identified a novel periosteal osteogenic progenitor subset that is active in jawbone osteogenesis and healing.