Pdgfrβ marks distinct mesenchymal and pericyte populations within the periosteum with overlapping cellular features

Abstract Platelet-derived growth factor receptor β (Pdgfrβ) is a cell surface marker often present on mesenchymal progenitor cells, playing a key role in regulating cell proliferation, migration, and survival. In the skeleton, Pdgfrβ-positive cells have significant osteogenic potential, differentiating into osteoblasts after injury to promote bone repair and homeostasis. However, multiple cell types within bone tissue express Pdgfrβ and their overlapping or distinct cellular features remain incompletely understood. Using a combination of single-cell RNA sequencing and transgenic Pdgfrβ-CreERT2-mT/mG reporter mice, we examined Pdgfrβ+ cells in mouse long bone periosteum. By single-cell analysis, Pdgfrb expression was found among a subset of mesenchymal cells and universally among pericytes within the periosteum. Histologic analysis of Pdgfrβ reporter activity confirmed a combination of perivascular and non-perivascular Pdgfrβ-expressing cell types. When isolated, Pdgfrβ reporter+ skeletal periosteal cells showed enhanced colony-forming, proliferative, migratory, and osteogenic capacities. Pdgfrβ reporter+ cells were further distinguished by co-expression of the pericyte marker CD146, which yielded Pdgfrβ+CD146+ pericytes and Pdgfrβ+CD146− skeletal mesenchymal cells. Colony forming and proliferative capacity were most highly enriched among Pdgfrβ+CD146+ pericytes, while osteogenic differentiation was similarly enriched across both Pdgfrβ+ cell fractions. In summary, Pdgfrβ expression identifies multiple subsets of progenitor cells within long bone periosteum with or without perivascular distribution and with overlapping cellular features.