Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastomaOACSTPCD
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.
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;
Hospital of Stomatology,Sun Yat-sen University,Guangzhou,China Guangdong Provincial Key Laboratory of Stomatology,Sun Yat-sen University,Guangzhou,China Guanghua School of Stomatology,Sun Yat-sen University,Guangzhou,ChinaDepartment of Periodontics,Affiliated Stomatology Hospital of Guangzhou Medical University,Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine,Guangzhou,ChinaInstitute for Advanced Study,Shenzhen University,Shenzhen,ChinaCenter for Translational Medicine,The First Affiliated Hospital,Sun Yat-sen University,Guangzhou,ChinaState Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou,ChinaDepartment of Oral and Maxillofacial Surgery,Nanfang Hospital,Southern Medical University,Guangzhou,ChinaDepartment of Oral and Maxillofacial&Head and Neck Oncology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China National Center for Stomatology,National Clinical Research Center for Oral diseases,Shanghai Key Laboratory of Stomatology,Shanghai,ChinaHospital of Stomatology,Sun Yat-sen University,Guangzhou,China Guangdong Provincial Key Laboratory of Stomatology,Sun Yat-sen University,Guangzhou,China
临床医学
inhibitedcyclingeliminated
《International Journal of Oral Science》 2024 (002)
P.251-264 / 14
supported by the National Natural Science Foundation of China(82141112);Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125/D-14);C.W.and the Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYLJ202112).
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