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 un...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.展开更多
Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a com...Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.展开更多
基金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).
文摘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.
基金supported by the National Natural Science Foundation of China(82141112,82073265)Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125/D-14)to C.W.
文摘Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
