Single-cell transcriptomics identifies PDGFRA+ progenitors orchestrating angiogenesis and periodontal tissue regeneration

作者：Jianing Liu, Junxi He, Ziqi Zhang, L N Liu, Yuan Cao, Xiaohui Zhang, Xinyue Cai, Xin Luo, Xiaocan Lei, Nan Zhang, Hao Wang, Ji Chen, Peisheng Liu, Jiongyi Tian, Jie-Xi Liu, Yuru Gao, Haokun Xu, Chao Ma, Shengfeng Bai, Yubohan Zhang, Yan Jin, Chenxi Zheng, Bing‐Dong Sui, Fang Jin · 发表于：International Journal of Oral Science · 年份：2025 · DOI：10.1038/s41368-025-00384-6 · 被引用次数：18 · 研究领域：dental development and anomalies、Bone and Dental Protein Studies、Proteoglycans and glycosaminoglycans research

Abstract Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA + dental follicle stem cells (DFSCs) and CD31 + Endomucin + endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA + DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA + DFSC aggregates and recipient EC...