1. Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China; 2. Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China; 3. Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China; 4. Department of Periodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, China; 5. Institute for Advanced Study, Shenzhen University, Shenzhen, China; 6. Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; 7. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China; 8. Department of Oral and Maxillofacial Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China; 9. Department of Oral and Maxillofacial & Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 10. National Center for Stomatology, National Clinical Research Center for Oral diseases, Shanghai Key Laboratory of Stomatology, Shanghai, China
2024-02-29
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Received
Published Online
2024-07-10
2024-07-10
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Abstract
Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.
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