Project description:We have employed whole genome microarray expression profiling as a discovery platform to identify genes that are associated with pathogenesis of ameloblastoma using ameloblastoma tumor and corresponding normal counterpart from patients.
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
Project description:Ameloblastoma is a locally aggressive odontogenic epithelial tumor with poorly understood intraosseous pathogenesis due to a lack of physiologically relevant models. Here, we established an orthotopic intraosseous mouse model using ameloblastoma epithelial cells in combination with ameloblastoma-derived mesenchymal stromal cells (AMMSCs) or their secretome. AMMSC-derived extracellular vesicle-enriched secretome enhances stemness, epithelial-mesenchymal transition (EMT) phenotypes, and tumorigenic ability of ameloblastoma epithelial cells. A unique signature of microRNAs in AMMSC-derived secretome is functionally associated with the upregulation of EMT-regulatory transcription factors in tumor epithelial cells. Single-nucleus ATAC and RNA sequencing revealed a dynamic EMT trajectory in primary human AM-derived epithelial cells activated by paired AMMSC-derived secretome. This study suggests that AMMSCs and their secretome drive orthotopic AM tumor development by promoting tumor epithelial cell proliferation, EMT, and vascular formation in the tumor microenvironment. This stromal-oriented orthotopic model provides a clinically relevant platform for dissecting tumor-stroma crosstalk and identifying therapeutic vulnerabilities in ameloblastoma.
Project description:To investigate the minimal genomic alterations in ameloblastoma, we have employed high-resolution CGH as a discovery platform to identify somatic genomic gains and losses in ameloblastoma tumors.