Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma

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Int J Oral Sci. 2024 Feb 29;16(1):21. 

Gan Xiong ^# 1 2 3, Nan Xie ^# 1 2 3, Min Nie ⁴, Rongsong Ling ⁵, Bokai Yun ^1 2 3, Jiaxiang Xie ^1 2 3, Linlin Ren ^1 2 3, Yaqi Huang ^1 2 3, Wenjin Wang ^1 2 3, Chen Yi ^1 2 3, Ming Zhang ^1 2 3, Xiuyun Xu ^1 2 3, Caihua Zhang ⁶, Bin Zou ⁷, Leitao Zhang ⁸, Xiqiang Liu ⁸, Hongzhang Huang ^1 2 3, Demeng Chen ⁶, Wei Cao ^9 10, Cheng Wang ^11 12 13

Affiliations expand

• PMID: 38424060
• PMCID: PMC10904398
• DOI: 10.1038/s41368-024-00281-4

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.