Requirement of Pdgfrα+ cells for calvarial bone repair

• Published in: Stem cells translational medicine Vol. 13; no. 8; pp. 791 - 802
• Main Authors: Xing, Xin, Li, Zhao, Xu, Jiajia, Chen, Austin Z, Archer, Mary, Wang, Yiyun, Xu, Mingxin, Wang, Ziyi, Zhu, Manyu, Qin, Qizhi, Thottappillil, Neelima, Zhou, Myles, James, Aaron W
• Format: Journal Article
• Language: English
• Published: England 16-08-2024
• Subjects: Animals; Bone Regeneration - physiology; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Skull - injuries; Skull - metabolism; single-cell RNA sequencing; calvarial bone; bone healing; platelet-derived growth factor receptor; skeletal cells; mesenchymal cells; bone repair
• ISSN: 2157-6564; 2157-6580; 2157-6580
• DOI: 10.1093/stcltm/szae041

Platelet-derived growth factor receptor α (PDGFRα) is often considered as a general marker of mesenchymal cells and fibroblasts, but also shows expression in a portion of osteoprogenitor cells. Within the skeleton, Pdgfrα+ mesenchymal cells have been identified in bone marrow and periosteum of long bones, where they play a crucial role in participating in fracture repair. A similar examination of Pdgfrα+ cells in calvarial bone healing has not been examined. Here, we utilize Pdgfrα-CreERTM;mT/mG reporter animals to examine the contribution of Pdgfrα+ mesenchymal cells to calvarial bone repair through histology and single-cell RNA sequencing (scRNA-Seq). Results showed that Pdgfrα+ mesenchymal cells are present in several cell clusters by scRNA-Seq, and by histology a dramatic increase in Pdgfrα+ cells populated the defect site at early timepoints to give rise to healed bone tissue overtime. Notably, diphtheria toxin-mediated ablation of Pdgfrα reporter+ cells resulted in significantly impaired calvarial bone healing. Our findings suggest that Pdgfrα-expressing cells within the calvarial niche play a critical role in the process of calvarial bone repair.