Mus musculus
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PROVIDER: PRJNA262048 | ENA |
REPOSITORIES: ENA
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Project description:OT-1 Transgenic CD8 T-cells were isolated from spleens of WT, PKCθ theta KO, and p50 cRel DKO mice. The T-cells were either cultured with non-pulsed DC (WT only and signified as "WT - UN") or with BMDCs pulsed with the OVA peptide SIINFEKL (N4) (WT, PKCθ theta KO, and p50 cRel DKO and signified as 'genotype - N4') at a ratio of 1:10 (DC:T-cell) for 18 hours. DCs then were depleted from the culture and RNA was made from the T-cells to measure gene expression at the early / late stage of T-cell activation
2014-12-01 | GSE61758 | GEO
Project description:NF-kB plays a crucial role in immunity to infection. This transcription factor consists in different combinatory homo- and hetero-dimers of the five members of the Rel family. cRel/p50-containing dimers have been involved in the development and function of the immune cells. However, the transcriptional roles of these two subunits still remain poorly explored in innate immune cells. By a multiple approach integrating ex vivo genomic analysis and an in vivo experimental study, we have investigated the consequences of the combined absence of cRel and p50 subunits of NF-kB in the innate response to infection. We have performed gene profiling of cRel-/-p50-/- (DKO) and wild type (WT) peritoneal macrophages stimulated with endotoxin for 2, 6 or 18 hours.
2012-11-21 | E-MEXP-3446 | biostudies-arrayexpress
Project description:Adaptive immune responses to infection result in the formation of memory T and B cells that respond more rapidly and robustly to reinfections, providing the basis of the immunological memory targeted by vaccines. Underlying the enhanced responsiveness of memory cells is their ability to rapidly up-regulate the transcription of key effector genes at a higher level compared to naïve cells (termed transcriptional memory). While transcriptionally permissive histone modifications are known to provide chromatin structures that facilitate transcriptional memory, the molecular mechanisms that underpin this process still remain elusive. The role of the cytoplasmic signalling kinase, PKC-θ in T cell signalling cascades is well established, however PKC-θ has also recently been described as a chromatin-modifying enzyme. We have previously demonstrated that PKC-θ forms a part of an active transcription complex that docks at the IL2 gene - a gene which displays transcriptional memory. In this study, we perturbed PKC-θ expression using approaches such as siRNA knockdown in primary human naïve and memory CD4+ T cells to show that transcriptional memory is highly dependent on PKC-θ, particularly in memory CD4+ T cells. Chromatin-tethered PKC-θ was immuno-precipitated with high levels of the activating marks, H3K4me3 and H3K9ac and low levels of the repressive mark, H3K27me3 at the IL2 promoter in ex vivo-derived, activated memory CD4+ T cells. Further ChIP-sequencing analysis revealed that PKC-θ was prevalent at transcriptionally permissive domains such as promoters, upstream regions and exons but also at intronic regions containing putative enhancers annotated to a subset of genes preferentially expressed in memory CD4+ T cells. Collectively, these data argue that chromatin-tethered PKC-θ can directly regulate genes to establish and maintain a permissive chromatin state that facilitates transcriptional memory in human CD4+ T cells.
2016-05-01 | GSE61241 | GEO
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.
| S-EPMC8784167 | biostudies-literature
Project description:Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-θ) regulates EMT by acting as a critical chromatin-anchored switch for inducible genes. Genome-wide transcriptome analysis identifies a unique cohort of inducible PKC-θ-sensitive genes in MCF7 cells stimulated with phorbol ester. MCF7 Cells treated with mock or siRNA against PKCtheta were left unstimulated or stimulated with PMA. No replicates.
2014-06-22 | E-GEOD-53267 | biostudies-arrayexpress
Project description:NFkB is a family of transcriptional factors that are responsible for inflammatory and immune gene expression. RelA, RelB and cRel are the transactivation domain containing family members. P50 encoded by Nfkb1 is the primary dimerization partner. Many NFkB deficient mice are embryonic lethal. In order to identify NFkB dependent genes, MEF were isolated from Rela-/-cRel-/-, Rela-/-cRel-/-Nfkb1-/- and Rela-/-Relb-/-cRel-/- embryos at E12.5. They were treated with 100ng/ml LPS for 1hr and then profiled gene expression by microarray.
2016-06-27 | E-MTAB-4412 | biostudies-arrayexpress
Project description:The breast tumour microenvironment (TME) includes fibroblasts, adipocytes, inflammatory and immune cells. While treatment of tumours with chemotherapeutic agents such as Docetaxel, leads to apoptosis of tumour cells, it can also have consequences for the cellular makeup and transcriptional profile of the TME and these, like increased epithelial mesenchymal transition can promote undesirable consequences, such as Cancer Stem Cell development. PKC-theta may have a role in these undesired effects. To be able to examine the effects of co-treatment of Docetaxel with an inhibitor of PKC-theta, we performed RNA-seq on tumours from mice injected with the human breast cancer cell line MDA-MB-231. We then separated reads mapped to the human and mouse genomes in silico, creating tumour and TME transcriptomes for control, Docetaxel, PKC-theta inhibitor and combination treated mice. Separation of the tumour and TME profiles illustrated a role for PKC-theta in the induction of a more basal-type transcriptome in the tumour, and of EMT in the TME.
2022-09-14 | GSE137467 | GEO
Project description:Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-θ) regulates EMT by acting as a critical chromatin-anchored switch for inducible genes. Genome-wide transcriptome analysis identifies a unique cohort of inducible PKC-θ-sensitive genes in MCF7 cells stimulated with phorbol ester.
2014-06-22 | GSE53267 | GEO
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
| S-EPMC4490682 | biostudies-literature