Project description:RNA sequencing was performed on biological triplicates of p53 null T-ALL cells with ZEB2 overexpression (P53/R26-Zeb2tg/tg) versus p53 null T-ALL cells without Zeb2 overexpression (P53/R26+/+) treated with 100nM GSK2879552 for 24h versus their corresponding DMSO treatment controls. P53/R26+/+ and P53/R26-Zeb2tg/tg tumor lines displayed a very distinct gene expression signature under baseline (DMSO) conditions in line with our previous observations that Zeb2 driven thymomas reflect a more immature T-ALL subtype. GSK2879552 is a potent, selective and orally bioavailable inhibitor of the lysine-specific histone demethylase 1 (LSD1). LSD1i treatment in control P53/R26+/+ cell lines only caused limited effects on overall transcription. In contrast, gene transcription was more severely affected by LSD1 perturbations in the P53/R26-Zeb2tg/tg lines with significant changes in the expression transcripts enriched for signalling pathways essential for embryonic development (like TGFbeta and Wnt signalling), genes involved in transcriptional repression/regulation, apoptosis and DNA replication/repair. All together, these results demonstrate that Zeb2 overexpression modulates murine T-ALL responsiveness to LSD1 inhibitors.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)