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This study focuses on the identification of the identity of oral facial mesenchymal stem/progenitor cells, using the oral facial bones of mice as the research object. Through single-cell RNA sequencing, the identification of the stromal cell clusters was completed, and combined with the analysis of cell communication and trajectory inference, the heterogeneity and functional differences of the cells were revealed. For the first time, the subpopulation of mesenchymal stem/progenitor cells expressing Smmhc in the early stage of the progenitor lineage was identified. The multi-directional differentiation potential of these cells was confirmed through in vivo lineage tracing, and the core regulatory role of this cell subpopulation in craniofacial bone development and tissue homeostasis was clarified through a targeted ablation model. Finally, the oral facial mesenchymal stem cell map was constructed, establishing the key position of Smmhc+ mesenchymal cells in craniofacial bone homeostasis.
Research Background
Reconstruction of craniofacial bone regeneration-related research faces clinical challenges. The specific identity and functional characteristics of oral facial mesenchymal stem/progenitor cells have not been fully defined, and there are gaps in the research on the heterogeneity and functional differences of subpopulations. This has become a key bottleneck restricting in-depth exploration in the field of oral facial bones, and it is urgent to fill the research gaps through precise classification and functional validation.
The tendon-bone transitional tissue has a highly specialized extracellular matrix structure, with the core feature being the hierarchical arrangement of collagen and the gradient composition of minerals. This structural system can achieve stable force transmission and guide the cell phenotype of spatial organization. Currently, it is impossible to precisely reproduce the complex multi-scale structure and composition gradient at the tendon-bone interface, which has become a key bottleneck hindering the integration of soft and hard tissue regeneration. It is urgently necessary to develop a biomimetic matrix construction scheme that conforms to the natural structure characteristics.
02 Main Content
This study focuses on the precise identification and functional validation of oral facial mesenchymal stem/progenitor cells, mainly exploring the existence characteristics, differentiation potential, and regulatory mechanisms of the mesenchymal stem/progenitor cell subpopulation expressing Smmhc in oral facial bone development and homeostasis. The heterogeneity of oral facial bone stromal cells was systematically analyzed, and the core role of key cell subpopulations in the ecological niche of craniofacial bone was clarified.
03 Research Design
1. Technical Methods: Single-cell RNA sequencing was used to detect the oral facial bone samples, and multiple types of stromal cell clusters were identified; a cell communication map was constructed and trajectory inference analysis was carried out to reveal the heterogeneity and functional differences of the cells.
2. Functional Validation: Using in vivo lineage tracing technology, the multi-directional differentiation potential of the mesenchymal stem/progenitor cells expressing Smmhc was verified; a SmmhcCreER;iDTR targeted ablation model was constructed to specifically eliminate the target cell subpopulation, and the effects on oral facial bone development and tissue homeostasis were observed.
04 Results
1. The precise classification of oral facial bone stromal cells was completed, and multiple stromal cell clusters were identified, clearly demonstrating the significant heterogeneity of oral facial mesenchymal stem/progenitor cells, and there were functional differences among different subpopulations.
2. In the earliest stage of the progenitor lineage, a previously unreported subpopulation expressing Smmhc of mesenchymal stem/progenitor cells was successfully identified; in vivo lineage tracing confirmed that this cell subpopulation has pluripotency and can differentiate into osteoblasts, osteocytes, periodontal ligament cells, and dental pulp cells, which are cells related to oral facial bones.
3. After targeted ablation of Smmhc+ mesenchymal stem/progenitor cells, the development of the oral facial bone was impaired, and the oral facial tissue homeostasis was disrupted, manifested as reduced bone formation and differentiation and abnormal non-cell-autonomous changes in the bone resorption process, confirming that this cell subpopulation is an indispensable core subset for maintaining craniofacial bone homeostasis.
4. The complete map of oral facial mesenchymal stem/progenitor cells was successfully constructed, systematically elucidating their heterogeneity characteristics and functional division.
05 Extension of Ideas
The oral facial mesenchymal stem cell map constructed in this study provides a core foundation for the in-depth exploration of the lineage differentiation mechanism of craniofacial bone cells and the regulatory network of bone homeostasis. Subsequent studies can focus on the regulatory pathways of this cell subset and the mechanisms of intercellular interactions, further expanding the research boundaries of the functional applications of oral and facial bone cell subsets, and providing more dimensions of theoretical support for basic research in the field of oral and facial bones. 4. Authors: Yi Fan, Yali Wei, Zhuoxuan Wu, Qin Huang, Chen Cui, Zucen Li, Ruoshi Xu, Quan Yuan, Chenchen Zhou
