Lepr‐Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1
Danting Zhang, Weimin Lin, Shuang Jiang, Peng Deng, Linfeng Liu, Qian Wang, Rui Sheng, Hui Sophie Shu, Lijun Wang, Weiguo Zou, Bo Zhou, Junjun Jing, Ling Ye, Bo Yu, Shiwen Zhang, Quan Yuan
Abstract
Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as a distinct periodontal ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs are located in the peri-vascular niche, possessing multilineage potential and contributing to tissue repair in response to injury. Ablation of Lepr+ PDLSCs disrupts periodontal homeostasis. Hyper-loading and unloading of occlusal forces modulate Lepr+ PDLSCs activation. Piezo1 is demonstrated that mediates the mechanosensing of Lepr+ PDLSCs by conditional Piezo1-deficient mice. Meanwhile, Yoda1, a selective activator of Piezo1, significantly accelerates periodontal tissue growth via the induction of Lepr+ cells. In summary, Lepr marks a unique multipotent PDLSC population in vivo, to contribute toward periodontal homeostasis via Piezo1-mediated mechanosensing.