Identification of Smmhc-expressing mesenchymal cells in orofacial bone at single-cell resolution

Abstract

Craniofacial bone regeneration remains a major clinical challenge, yet the identity of orofacial mesenchymal stem/stromal cells (OMSCs) has not been fully elucidated. Here, we performed single-cell RNA sequencing (scRNA-seq) on mouse orofacial bone and identified multiple stromal cell clusters. Cell-cell communication mapping and trajectory inference uncovered the heterogeneity of OMSCs and functional divergence among subpopulations. We identified a previously unrecognized population, Smmhc-expressing mesenchymal stem/stromal cells (MSCs), at the earliest stage of the progenitor lineage trajectory. In vivo lineage tracing demonstrated that Smmhc⁺ MSCs are multipotent, giving rise to osteoblasts, osteocytes, periodontal ligament (PDL) cells, and dental pulp cells. Targeted ablation of Smmhc⁺ MSCs using Smmhc^CreER;iDTR mouse model led to impaired orofacial bone development and disrupted orofacial tissue homeostasis, characterized by reduced osteogenic differentiation and non-cell autonomous reduction of bone resorption. Collectively, this study establishes a cellular atlas of OMSCs and identifies Smmhc⁺ MSCs as a functionally indispensable subset for craniofacial bone homeostasis, orchestrating the dynamic balance between osteogenesis and bone resorption within the orofacial skeletal niche.

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Funding

National Natural Science Foundation of China (National Science Foundation of China)(82171001)

Natural Science Foundation of Sichuan Province(2024NSFSC0545) Youth Innovation Project of Sichuan Province (Q23007) Research Funding from West China School/Hospital of Stomatology, Sichuan University (RCDWJS2024-4)

RIGHTS & PERMISSIONS

The Author(s)