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Although mouse models are widely used to study wound healing and various diseases, their translational relevance remains unclear. Here, we performed a comparative single\u2010cell transcriptomic analysis of human and mouse oral mucosa to identify both shared and species\u2010specific mechanisms. A total of 34,969 cells from human and mouse datasets were integrated using Harmony for batch effect correction, allowing us to establish a unified oral mucosa transcriptome atlas. Fibroblasts emerged as the prominent cell population in both species, displaying conserved gene expression profiles and cell communication networks, underscoring their central role in tissue homeostasis. Key pathways involved in extracellular matrix remodelling and wound healing were highly conserved, supporting the utility of mouse models for studying fibroblast\u2010mediated tissue regeneration. These findings suggest that mouse models can effectively replicate human fibroblast biology, offering valuable insights for developing translational therapies that target fibroblast activity and regulatory gene networks to enhance wound healing and tissue regeneration. Additionally, we identified species\u2010specific cell populations, including human\u2010specific capillary endothelial cells and melanocytes, as well as mouse\u2010specific salivary gland epithelial cells. Their distinct cellular composition and functional differences suggest that these subpopulations may not be directly translatable from mouse models to human contexts. Overall, our study highlights the evolutionary conservation of fibroblasts while identifying species\u2010specific differences that warrant consideration in translational research. These findings provide a valuable resource for researchers using mouse models to study oral mucosa\u2010related diseases, facilitating the translation of preclinical discoveries into clinical applications.<\/jats:p>","DOI":"10.1111\/jcmm.70768","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T03:53:37Z","timestamp":1754106817000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Delineating Tissue\u2010Specific Cell Identity of Oral Mucosa in Humans and Mice From a Single\u2010Cell Perspective"],"prefix":"10.1111","volume":"29","author":[{"given":"Huanyu","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Oral Biology, School and Hospital of Stomatology Jilin University  Changchun China"},{"name":"Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School and Hospital of Stomatology Jilin University  Changchun China"},{"name":"Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, School and Hospital of Stomatology Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0360-7388","authenticated-orcid":false,"given":"Zhengwen","family":"An","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School and Hospital of Stomatology Jilin University  Changchun China"},{"name":"Key Laboratory of Tooth Development and Bone Remodeling of Jilin Province, School and Hospital of Stomatology Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07039"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.682143"},{"issue":"11","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041244","article-title":"Intrinsic Networks Regulating Tissue Repair: Comparative Studies of Oral and Skin Wound Healing","volume":"14","author":"Overmiller A. 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