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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\n                    <jats:sup>+<\/jats:sup>\n                    MSCs are multipotent, giving rise to osteoblasts, osteocytes, periodontal ligament (PDL) cells, and dental pulp cells. Targeted ablation of Smmhc\n                    <jats:sup>+<\/jats:sup>\n                    MSCs using\n                    <jats:italic>Smmhc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>CreER<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>;iDTR<\/jats:italic>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    MSCs as a functionally indispensable subset for craniofacial bone homeostasis, orchestrating the dynamic balance between osteogenesis and bone resorption within the orofacial skeletal niche.\n                  <\/jats:p>","DOI":"10.1038\/s41413-026-00518-4","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T02:55:00Z","timestamp":1774234500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Smmhc-expressing mesenchymal cells in orofacial bone at single-cell resolution"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7511-9872","authenticated-orcid":false,"given":"Yi","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoxuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zucen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoshi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6427-5869","authenticated-orcid":false,"given":"Chenchen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"518_CR1","doi-asserted-by":"publisher","first-page":"109858","DOI":"10.1016\/j.msec.2019.109858","volume":"103","author":"Q Zhang","year":"2019","unstructured":"Zhang, Q. et al. 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