Wenjing Yu
| Wenjing Yu |
Wenjing Yu1, Xuefeng Zhao1, Chun-Hsi Chung1, Chider Chen2
1Orthodontics, University of Pennsylvania, School of Dental Medicine, 2Oral & Maxillofacial Surgery & Pharmacology, University of Pennsylvania, School of Dental Medicine
Introduction
Rapid maxillary expansion is widely used by orthodontists in treating transverse deficient patients. However, patients responded differently to maxillary expansion, especially in adult group. Although it is proposed that differences in calcification patterns of the mid-palatal suture, craniofacial architecture, and age are contributing factors, the biological basis underlying maxillary expansion is not well understood. Mesenchymal stem cell (MSC) refers to a group of heterogeneous multipotent stem cells that can self-renew and further differentiate into several cell types, including osteoblasts, chondrocytes, and adipocytes, which plays an important role in bone remodeling. Cell population within mid-palatal suture and cellular and molecular mechanisms in response to mechanical stimuli are potential factors other than the calcification patterns, craniofacial architecture, and patient’s age. The goal of this study is to investigate the roles of stem cells resided in mid-palatal suture and their interplay with surrounding immune cells during maxillary expansion.
Methods
Maxillary mid-palatal expansion model was established using 6 weeks old Gli1-CreERT2 mice. After 10-day expansion, cells isolated from mid-palatal suture were used for flow cytometry analysis, single-cell RNA sequencing, and MSC culture. Maxilla tissue was harvested for micro-computed tomography (CT) analysis, H&E staining and immunofluorescent imaging.
Results
Mid-palatal suture-MSCs were labeled by red fluoresces using Gli1-CreERT2 mice after exposed to tamoxifen. Maxillary expansion promoted the proliferation of the Gli1+ suture-MSCs. In addition, our results revealed that the osteogenesis of MSCs isolated from maxillary expanded mice was significantly elevated, indicating mechanical force enhances endogenous stem cell expansion and osteogenic differentiation for de novo bone formation. Single cell transcriptomics identified not only MSC lineage trajectories shifted in response to expansion stimuli, but also the effects from immune cells, such as neutrophils, guided MSC reconfiguration toward active immunomodulation.
Conclusion
Our data provided the evidence to show presence of MSCs within mid-palatal suture, which is critical to govern bone remodeling under maxillary expansion. MSC lineage trajectories and the unique immune microenvironment have been revealed by single cell transcriptomics to depict the interplay between stem cells and surrounding immune microenvironment within mid-palatal suture.