Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Int J Oral Sci. 2024 Feb 29;16(1):21. doi: 10.1038/s41368-024-00281-4.
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.
成釉细胞瘤是一种良性肿瘤，其具有局部侵袭性表型，导致面部骨破坏和高复发率。然而，肿瘤发生和复发的机制仍不清楚。在这里，我们在单细胞分辨率下揭示了成釉细胞瘤复发的细胞景观和机制。我们的结果表明，成釉细胞瘤表现出五种肿瘤亚群，分别与免疫反应 (IR)、骨重塑 (BR)、牙齿发育 (TD)、上皮发育 (ED) 和细胞周期 (CC) 特征有关。值得注意的是，我们发现 CC 成釉细胞瘤细胞具有干性，并有助于肿瘤复发，这主要由 EZH2 介导的程序控制。靶向 EZH2 可有效消除 CC 成釉细胞瘤细胞，并抑制成釉细胞瘤患者来源的类器官中的肿瘤生长。这些数据描述了肿瘤亚群，并阐明了 CC 成釉细胞瘤细胞的特性、功能和调控机制，为成釉细胞瘤提供了一个潜在的治疗靶点。
