PDF(Pubmed)
Abstract：
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.
摘要：
血小板衍生生长因子受体α(PDGFRα)通常被认为是间充质细胞和成纤维细胞的一般标志物,但也显示在一部分骨祖细胞中的表达。在骨架内，已经在长骨的骨髓和骨膜中鉴定出Pdgfrα间质细胞，它们在参与骨折修复中起着至关重要的作用。尚未对颅骨愈合中的Pdgfrα细胞进行类似的检查。这里,我们利用Pdgfrα-CreERTM;mT/mG报告动物通过组织学和单细胞RNA测序（scRNA-Seq）检查Pdgfrα+间充质细胞对颅骨修复的贡献。结果表明，通过scRNA-Seq，Pdgfrα+间充质细胞存在于多个细胞簇中，通过组织学，Pdgfrα细胞的急剧增加在早期时间点填充了缺损部位，从而导致骨组织随时间愈合。值得注意的是,白喉毒素介导的Pdgfrα报告细胞消融导致颅骨愈合显着受损。我们的发现表明，颅骨小生境中表达Pdgfrα的细胞在颅骨修复过程中起着至关重要的作用。
