Project description:Chromosome instability (CIN) leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes affecting two out of three cancers. Continuous CIN in murine T-cells was previously shown to dramatically accelerate lymphomagenesis in a p53-deficient background. Despite the predicted ongoing CIN in our mouse model, we observed whole chromosome copy number changes that affected all lymphoma cells, suggesting that CIN is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes outcompetes the CIN-imposed missegregation. To distinguish between these explanations and to examine karyotype dynamics in CIN lymphoma, we used a newly developed single-cell whole genome-sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. In this study we applied single cell whole genome sequencing (scWGS) to map and quantify karyotype heterogeneity in primary mouse lymphoma and human leukaemia samples. We used cohorts of Mps1f/f; Lck-Cre+, Mps1f/f; p53f/f; Lck-Cre+ and Mps1f/f; p53f/+; Lck-Cre+ mice, and Lck-Cre- mice as controls. Mice were sacrificed when exhibiting signs of lymphoma (10-14 weeks of age, typically dyspnoea due to an enlarged thymus), thymuses were harvested, and primary T-ALL single cell suspensions were frozen for subsequent single cell sequencing analysis.
Project description:Myristic acid, the 14-carbon saturated fatty acid (C14:0), is usually associated with negative consequences for human health, and in particular its consumption is correlated to an increased cardiovascular disease risk. Since it is a little abundant into the cells, its specific properties and functional roles have not been fully described. The aim of this study was to explore the cell response to this fatty acid to help explaining clinical findings on the relationship between C14:0 and cardiovascular disease. Primary murine hepatocytes were used as a model to investigate the hepatic response to C14:0 in a proteomic approach. C14:0 treatment (250 µM) of primary murine hepatocytes confirmed that myristic acid induces lipid droplet accumulation as shown by cellular imaging and elevated perilipin 2 levels on cellular proteome level. The functionally enriched pathways were involved in protein synthesis, transport and degradation, protein depalmitoylation, unfolded protein response, lipid and cholesterol metabolism, mitophagy in response to depolarization, and cell cell adhesion. Our data provide for the first time quantitative proteomic data regarding C14:0 in primary murine hepatocytes (M1 in present dataset) and contribute to the elucidation of the molecular mechanisms through which this fatty acid can cause adverse health effects.
Project description:We performed single cell RNA sequencing of Epcam+ sorted cells from murine prostate cancer models to characterize the epithelial compartment of the tumors.
Project description:Single cell RNA-seq was performed on dissected murine ciliary body samples, and the resulted sequencing data was used to assess the various cell types present within the dissected tissue