This SuperSeries is composed of the SubSeries listed below.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesSox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesJoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Specimen part, Cell line
View SamplesPolarization of macrophages to M1 or M2 cells is important for mounting responses against bacterial and helminth infection respectively. Jumonji domain containing 3 (JMJD3), a histone 3 K27 demethylase, has been implicated in the activation of macrophages. Here we show that JMJD3 is essential for M2 macrophage polarization to helminth infection and chitin, though JMJD3 is dispensable for M1 responses. Furthermore, Jmjd3 is critical for proper bone marrow macrophage differentiation in a demethylase activity-dependent manner. Jmjd3 deficiency affected trimethylation of H3K27 in only a limited numbers of genes. Among them, we identified Irf4 as the target transcription factor critical for controlling M2 macrophage polarization. Collectively, these results show that JMJD3-mediated H3K27 demethylation is critical for regulating M2 macrophage development leading to anti-helminth host responses.
The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity.
Specimen part
View SamplesThe transcriptomics changes induced in Primary Mouse Hepatocytes by Cyclosporin A after treatment for 24h and 48h
Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity.
Specimen part
View SamplesEnhanced prenatal fatty streak formation in human fetuses has been associated with maternal hypercholesterolemia. However, the possible roles of maternal genetic background and in utero environment on development of atherosclerosis in adult life have not been unraveled. We generated genetically identical heterozygous apoE-deficient mice offspring with a different maternal background to study the intrauterine effect of maternal genotype and associated hypercholesterolemia on the developing vascular system. As read out for increased atherosclerosis development in adult life, a constrictive collar was placed around the carotid artery to induce lesion formation. A significant increase in endothelial cell activation and damage was detected in the carotid arteries of heterozygous apoE-deficient fetuses with apoE-deficient mothers compared with offspring from wild type mothers, but no fatty streak formation was observed. Postnatally, all carotid arteries revealed normal morphology. In adult offspring with maternal apoE-deficiency, the constrictive collar resulted in severe lesion (9/10) development compared with no to only minor lesions (2/10) in offspring of wild type mothers. Microarray analysis showed no effect of maternal apoE-deficiency on gene expression in adult offspring. We conclude that maternal apoE-deficiency not only affects fetal arteries, but also increases the susceptibility for development of collar-induced atherosclerosis in adult life.
Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life.
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View SamplesGlucocorticoids control expression of a large number of genes after binding to the glucocorticoid receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive.
Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor.
Sex, Specimen part
View SamplesThe functioning of a specific tissue depends on the expression pattern of the different genes. We used microarrays to compare gene expression across different murine tissues, to get a better understanding in the expression pattern and functioning of the different tissues. With this analysis, we were not only able to identify genes that were specifically expressed in a spicific tissue but, as important, we also identified genes that were specifically repressed in a tissue, compared to al the other analysed tissues.
Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.
Specimen part
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