Gan Xiong, Nan Xie, Min Nie, Rongsong Ling, Bokai Yun, Jiaxiang Xie, Linlin Ren, Yaqi Huang, Wenjin Wang, Chen Yi, Ming Zhang, Xiuyun Xu, Caihua Zhang, Bin Zou, Leitao Zhang, Xiqiang Liu, Hongzhang Huang, Demeng Chen, Wei Cao, Cheng Wang
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引用次数: 0
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.
釉母细胞瘤是一种良性肿瘤,其特点是局部侵袭性表型,导致面部骨骼破坏和高复发率。然而,人们对肿瘤发生和复发的机制知之甚少。在这里,我们以单细胞分辨率揭示了导致母细胞瘤肿瘤复发的细胞景观和机制。我们的研究结果显示,母细胞瘤表现出五个肿瘤亚群,它们在免疫反应(IR)、骨重塑(BR)、牙齿发育(TD)、上皮发育(ED)和细胞周期(CC)特征方面各不相同。值得注意的是,我们发现CC骨髓母细胞瘤细胞具有干性并导致肿瘤复发,而肿瘤复发是由EZH2介导的程序主导的。靶向 EZH2 能有效消除 CC 骨髓母细胞瘤细胞,并抑制骨髓母细胞瘤患者衍生的器官组织中的肿瘤生长。这些数据描述了肿瘤亚群,阐明了CC母细胞瘤细胞的特性、功能和调控机制,为治疗母细胞瘤提供了一个潜在的治疗靶点。
期刊介绍:
The International Journal of Oral Science covers various aspects of oral science and interdisciplinary fields, encompassing basic, applied, and clinical research. Topics include, but are not limited to:
Oral microbiology
Oral and maxillofacial oncology
Cariology
Oral inflammation and infection
Dental stem cells and regenerative medicine
Craniofacial surgery
Dental material
Oral biomechanics
Oral, dental, and maxillofacial genetic and developmental diseases
Craniofacial bone research
Craniofacial-related biomaterials
Temporomandibular joint disorder and osteoarthritis
The journal publishes peer-reviewed Articles presenting new research results and Review Articles offering concise summaries of specific areas in oral science.