Project description:Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes. Tumors arising from bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to tumors arising from the inoculation of high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats.
Project description:We have profiled by RNA-sequencing healthy livers and 4 distinct murine intrahepatic cholangiocarcinoma (iCCA) models to compare their molecular profile to the identified human STIM clusters of iCCA. Results: Comparative analysis indicated high molecular similarity between the KRAS/p19 model and the human Inflammatory stroma cluster while the other models resembled the Hepatic stem-like cluster.
Project description:Here we analyzed mouse and human samples to characterize origin, subtypes, functions and cell-cell interactions of cancer-associated fibroblasts in cholangiocarcinoma, a highly desmoplastic tumor of the liver. Hepatic stellate cell-derived cancer-associated fibroblasts were isolated from two different models of murine intrahepatic cholangiocarcinoma, induced by overexpression of YAP+AKT or KRASG12D in combination with sg-p19, and compared by bulk RNA-sequencing to hepatic stellate cells from two models of liver fibrosis, induced by bile duct ligation or DDC diet. CAF-enriched fractions of from YAP+AKT or KRAS/sg-p19-induced intrahepatic cholangiocarcinoma, were analyzed by single-cell RNA sequencing. A cell suspension from human cholangiocarcinoma, containing all cell populations, was analyzed by single cell RNA-sequencing.
Project description:Cholangiocarcinoma (CCA) is a deadly tumour lacking effective therapies. Clinically-relevant experimental models and analysis of human samples represent the cornerstone of mechanistic cancer research. Thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats encompasses key histological and molecular features of human iCCA. Molecular studies in bile may capture carcinogenic alterations and therapeutic vulnerabilities in CCA. We performed bile proteomic and metabolomic analyses in this model leading us to identify unrecognized mechanisms relevant to human iCCA.
Project description:B cell-interacting reticular cells (BRC) form transcriptionally and topologically stable immune-interacting microenvironments that direct efficient humoral immunity. While several immune niche factors have been elucidated, the cues sustaining BRC function and topology across activation states remain unclear. Here, we employed spatial transcriptome analysis of murine ingunal and mesenteric lymph nodes to examine co-localization of distinct BRC subsets and immune cells complementing BRC-immune cell interaction analysis. Spatial analysis supported predicted feedforward BRC-immune cell circuits that sustain topologically-organized, functional niches across inflammatory states, lymphoid organs and species.
Project description:Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes.
2012-06-21 | GSE38834 | GEO
Project description:WES of murine syngeneic models
| PRJNA506146 | ENA
Project description:RNASeq of murine syngeneic models
Project description:We created new mouse mammary tumor models to identify biomarkers of sensitivity to immune checkpoint inhibitors. Using these models in a syngeneic transplant system and treating with anti-PD1/anti-CTLA4 combination therapy, we profiled treated and non-treated tumors by RNA-SEQ. Herein, the profiled tumors represent models that are resistant or senstitive to immune checkpoint inhibitors at distinct timepoints of therapy and tumor progression.
