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At the same time, there is an urgent need to understand the key cell subtypes that determine the clinical subtypes. We characterized the single-cell transcriptional profiles of clinical subtypes of AM. We also characterized a pseudotime transition trajectory from immunoactive epithelial cells to vascular-associated fibroblasts, identifying key transcription factors involved in this process. Notably, we observed significant heterogeneity between M1 and M2 macrophages among the clinical subtypes of AM. Furthermore, our analysis revealed that metabolic disorder in AM was primarily driven by the metabolic disturbances in M1 and M2 macrophages. At the cellular communication level, we highlighted the role of M2 macrophages in mediating cell interactions, focusing on the RANKL\/RANK pathway associated with osteoclast activity. Finally, we attempted to establish a unicystic AM\u2013derived epithelial cell line and utilized it to construct an AM-like organoid model; we found that M2 macrophages competed with AM for L-cysteine to achieve cystic changes in the solid lesion. Our exploration of pathogenesis underlying various clinical types of AM advances our knowledge of AM heterogeneity, offering promising targets for novel therapeutic strategies.<\/jats:p>","DOI":"10.1177\/00220345251340892","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T02:22:11Z","timestamp":1750990931000},"page":"1506-1516","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Single-Cell Insights into Unicystic and Solid Ameloblastoma Heterogeneity"],"prefix":"10.1177","volume":"104","author":[{"given":"C.","family":"Feng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral &amp; Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School &amp; Hospital of Stomatology, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Dou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral &amp; 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