Project description:To map gene regulation downstream of cholesterol overload and NF-kappaB signaling in smooth muscle cells (SMCs), we cultured primary aortic SMCs from wildtype mice with cyclodextrin-complexed cholesterol or the prototypical NF-kappaB activator, tumor necrosis factor (TNF), or both.
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)
Project description:Smooth muscle differentiation has been proposed to sculpt airway epithelial branches in mammalian lungs. Serum response factor (SRF) acts with its cofactor myocardin to promote the expression of contractile smooth muscle markers. However, smooth muscle cells exhibit a variety of phenotypes beyond contractile that are independent of SRF-myocardin-induced transcription. To determine whether airway smooth muscle exhibits phenotypic plasticity during embryonic development, we deleted Srf from the pulmonary mesenchyme. Srf-mutant lungs branch normally, and the mesenchyme exhibits normal cytoskeletal features and patterning. scRNA-seq revealed an Srf-null smooth muscle cluster wrapping the airways of mutant lungs that lacks contractile smooth muscle markers but retains many features of control smooth muscle. Srf-null airway smooth muscle exhibits a synthetic phenotype, compared to the contractile phenotype of wildtype airway smooth muscle. Our findings reveal plasticity in mesenchymal differentiation during lung development and demonstrate that a synthetic smooth muscle layer is sufficient for airway branching morphogenesis.
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.