The goal of this experiment is to define how lack of Ikaros impacts gene expression in mature CD4 T cells, both in the resting and activated state. To do this, a conditional knockout mouse model was generated using Cre/lox technology. The floxed allele was designed such that the last translated exon and 3' UTR of the Ikaros gene (Ikzf1) are deleted in mature T cells (mediated by distal Lck-driven Cre). CD4 T cells from mice with floxed alleles that did not express Cre (Cre-) and those that did express Cre (Cre+) were analyzed.
Lack of Ikaros Deregulates Inflammatory Gene Programs in T Cells.
Specimen part
View SamplesFrom over 300 patients two groups were selected which had prostate tumors with either well differentiated (WD) or poorly differentiated (PD) after radical Prostatectomy. The PD group had Gleason score 8-9, seminal vesicle invasion, and poorly differentiated tumor cells; the WD group had Gleason score 6-7, no seminal vesicle invasion, and well to moderately differentiated tumor cells. LCM compatible specimens were selected from age and race (Caucasians) matched PD or WD patients with no family history of CaP. Matching normal epithelal cells were also selected for the analysis.
Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression.
Specimen part
View SamplesButyrate induces Treg via HDACi activity
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesMicroarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesMicroarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesExpression of the EMT-inducing transcription factor Snail is enhanced in different human cancers. To investigate the in vivo role of Snail during progression of epithelial cancer, we used a mouse model with skin-specific overexpression of Snail. Snail transgenic mice spontaneously developed distinct histological subtypes of skin cancer, such as basal cell carcinoma, squamous cell carcinoma and sebaceous gland carcinoma. Development of sebaceous gland carcinomas strongly correlated with the direct and complete repression of Blimp-1, a central regulator of sebocyte homeostasis. Snail expression in keratinocyte stem cells significantly promotes their proliferation associated with an activated FoxM1 gene expression signature, resulting in a larger pool of Mts24-marked progenitor cells. Furthermore, primary keratinocytes expressing Snail showed increased survival and strong resistance to genotoxic stress. Snail expression in a skin-specific p53-null background resulted in accelerated formation of spontaneous tumours and enhanced metastasis. Our data demonstrate that in vivo expression of Snail results in de novo epithelial carcinogenesis by allowing enhanced survival, expansion of the cancer stem cell pool with accumulated DNA damage, a block in terminal differentiation and increased proliferation rates of tumour-initiating cells.
Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential.
Sex, Age, Specimen part
View SamplesThe transcription factor Foxp3 is indispensible for the differentiation and function of regulatory T cells (Treg cells). To gain insights into the molecular mechanisms of Foxp3 mediated gene expression we purified Foxp3 complexes and explored their composition. Biochemical and mass-spectrometric analyses revealed that Foxp3 forms multi-protein complexes of 400-800 kDa or larger and identified 361 associated proteins ~30% of which are transcription-related. Foxp3 directly regulates expression of a large proportion of the genes encoding its co-factors. Reciprocally, some transcription factor partners of Foxp3 facilitate its expression. Functional analysis of Foxp3 cooperation with one such partner, Gata3, provided further evidence for a network of transcriptional regulation afforded by Foxp3 and its associates to control distinct aspects of Treg cell biology.
Transcription factor Foxp3 and its protein partners form a complex regulatory network.
Specimen part
View SamplesAdipose inflammation is a key component of cardiometabolic disease. We used microarray to profile gene expression changes in adipose tissue following administration of LPS (3ng/kg IV) to healthy human volunteers.
Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans.
Specimen part
View SamplesPersons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may serve as a useful model to examine potential factors responsible for DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile experiments revealed normal force generation of unfatigued Ts65Dn soleus, but a 12% reduction in force was observed in Ts65Dn muscle during recovery following fatiguing contractions compared to WT muscle (p<0.05). Oxidative stress may contribute to DS-related pathologies, including muscle weakness, which may be the result of overexpression of chromosome 21 genes (e.g., copper-zinc superoxide dismutase (SOD1)). SOD1 expression was 25% higher (p<0.05) in Ts65Dn soleus compared to WT muscle but levels of other antioxidant proteins were unchanged. Lipid peroxidation (4-hydroxynoneal) was unaltered in Ts65Dn muscle although protein carbonyls were 20% greater compared to muscle of WT animals (p<0.05). Cytochrome c oxidase expression was reduced 22% in Ts65Dn muscle, suggesting a limitation in mitochondrial function may contribute to post-fatigue muscle weakness. Microarray analysis of Ts65Dn soleus revealed alteration of numerous cellular pathways including: proteolysis, glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In summary, the Ts65Dn mouse displays evidence of muscle dysfunction, and the potential role of mitochondria and oxidative stress warrants further investigation.
Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition.
Sex, Age, Specimen part
View Samples