Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyze by RNAseq the gene expression profile of DN3 thymocytes from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice. GSEA analysis show a significant enrichment of MYC signature genes, consistent with a deficient function of NMe in GATA site 1 and 2 homozygous mutant thymocytes.
Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyze chromatin accessibility by ATACseq in DN3 thymocytes and Notch-induced TALL blasts from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice.
Project description:The NOTCH1-driven MYC enhancer (NMe) is essential for T cell development, transformation and the development of acute lymphoblastic leukemia. Here we analyzed by single-cell RNAseq the gene expression profile of total thymus from NMe wild type and NMe GATA site 1 and 2 (GS1+2) homozygous mutant mice.
Project description:We investigated the cause of gastrointestinal neoplasia in a man who developed adenocarcinoma of the ampulla of Vater at the age of 34, followed almost three decades later by adenomatous polyps and invasive adenocarcinomas of both the colon and stomach. Premature chromatid separation, mosaic variegated aneuploidy (MVA), combined with structural chromosome abnormalities were detected in his cells. We identified a homozygous intronic mutation, c.2386-11A>G in BUB1B which creates a de novo splice site that is favored over the authentic site. This study expands the phenotype of BUB1B mutations and MVA to include common adult-onset cancers and provides evidence for the interdependency of APC and BUBR1 proteins in humans.
Project description:Themis1, a recently described T-lineage specific protein, is essential for thymic positive and negative selection. Although Themis1 has been clearly identified as a component of the T cell antigen receptor (TCR) signalosome, its precise role in TCR signaling remains unclear. Here, we used quantitative proteomic and TCR signaling reporter mice to gain insight into Themis1 signaling function. Mass spectrometry analysis of the Themis1 interactome identified Grb2, SHP1 and Vav1 as the principal interacting partners of Themis1 in thymocytes. The dataset contains mass spectrometry results from the analysis of 6 different kind of AP-MS purifications (based on immunoprecipitation using a Themis1 antibody) starting from the following samples: - thymocytes from WT mice, non stimulated (noted WT NS) - thymocytes from WT mice, stimulated with pervanadate (noted WT P) - thymocytes from GRB2 +/- mice (with decreased expression of GRB2), non stimulated (noted GRB2 NS) - thymocytes from GRB2 +/- mice (with decreased expression of GRB2), stimulated with pervanadate (noted GRB2 P) - thymocytes from Themis1 -/- mice (knock-out for Themis1), non stimulated (noted KO NS) - thymocytes from Themis1 -/- mice (knock-out for Themis1), stimulated with pervanadate (noted KO P) Three biological replicates were prepared for these 6 different conditions (noted, 1,2,3), yielding 18 analyzed samples. Three technical nanoLC-MS runs were acquired for each sample (noted R1, R2, R3), leading to the 54 nanoLC-MS raw files contained in the dataset.