To attain deeper insight into metabolic alterations in Trpm6 gene deficient mice we used microarrays for profiling of hepatic transcripts of Trpm6 ko and control mice.
Epithelial magnesium transport by TRPM6 is essential for prenatal development and adult survival.
Sex, Age
View SamplesEmbryos were collected, aged, mock-treated/treated with 40Gy gamma radiation, and allowed to recover for 1.5 hours. Targets from 3 sets of wild type (yw, w1118) and 2 sets of mutant (Dmp53NS) biological replicates were generated and the expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with radiation-responsive and Dmp53-dependent expression patterns.
p53 directs focused genomic responses in Drosophila.
No sample metadata fields
View SamplesKc167 cells were mock-treated/treated with combinations of steroid hormone ecdysone and gamma-irradiation, and harvested. The expression profiles were determined using Affymetrix Drosophila Genechip 1 arrays. Comparisons between the sample groups allow the identification of genes with ecdysone- and/or radiation-responsive expression patterns.
p53 directs focused genomic responses in Drosophila.
No sample metadata fields
View SamplesLoss of Ck1alpha produces 'flyabetic' larvae that are feeding defective. In addition we found other larvae with glucose elevations show feeding aversion.
Circulating glucose levels inversely correlate with <i>Drosophila</i> larval feeding through insulin signaling and SLC5A11.
Sex, Specimen part
View SamplesTumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells.
Genome-wide profiling reveals stimulus-specific functions of p53 during differentiation and DNA damage of human embryonic stem cells.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma.
Cell line
View SamplesLittle is known about the epigenomics of liposarcoma (LPS). Here, we profiled the global expression of 9 epigenetic marks in well differentiated (WD) and dedifferentiated (DD) LPS from 151 patients and found increased H3K9me3 among DDLPS tumors. We performed ChIP-seqand gene expression profiling of patient derived cell lines to discover functionally significant regions of differential H3K9me3 enrichment between WDLPS and DDLPS associated with concomitant gene expression changes.
Increased H3K9me3 drives dedifferentiated phenotype via KLF6 repression in liposarcoma.
Cell line
View SamplesAsthma is a complex, chronic respiratory disease with marked clinical and pathophysiological heterogeneity. Distinct inflammatory phenotypes of eosinophilic, mixed, neutrophilic and paucigranulocytic asthma are identified in patients, but most in vivo mouse models, studying asthma mechanisms, mimic only eosinophilic phenotype in humans. The detailed unbiased in vivo studies on molecular responses among different kinds of inflammation in asthma models are lacking. Therefore, we developed mouse models representing three different inflammatory phenotypes of airway inflammation, namely eosinophilic, mixed, and neutrophilic asthma via different methods of house dust mite sensitisation.
Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice.
Specimen part
View SamplesPurpose: berrantly high expression of TRIM24 occurs in human cancers, including hepatocellular carcinoma. In contrast, TRIM24 in the mouse is reportedly a liver-specific tumor suppressor. To address this dichotomy and uncover direct regulatory functions of TRIM24 in vivo, we developed a new mouse model that lacks expression of all Trim24 isoforms, as the previous model expresses normal levels of Trim24 lacking only exon 4. Methods: To produce germline-deleted Trim24dlE1 mice, deletion of the promoter and exon 1 of Trim24 was induced in Trim24LoxP mice by crossing with a zona pellucida 3-Cre line for global deletion. Liver-specific deletion (Trim24hep) was achieved by crossing with an Albumin-Cre line. Phenotypic analyses were complemented by protein, gene-specific and global RNA expression analyses and quantitative chromatin immunoprecipitation. Results:Global loss of Trim24 disrupted hepatic homeostasis in 100% of mice with highly significant, decreased expression of oxidation/reduction, steroid, fatty acid and lipid metabolism genes, as well as increased expression of genes in unfolded protein, endoplasmic reticulum stress and cell cycle pathways. Trim24dlE1/dlE1 mice have markedly depleted visceral fat and, like Trim24hep/hep mice, spontaneously develop hepatic lipid-filled lesions, steatosis, hepatic injury, fibrosis and hepatocellular carcinoma. Conclusions: TRIM24, an epigenetic co-regulator of transcription, directly and indirectly represses hepatic lipid accumulation, inflammation, fibrosis and damage in the murine liver. Complete loss of Trim24 offers a model of human nonalcoholic fatty liver disease, steatosis, fibrosis and development of hepatocellular carcinoma in the absence of high-fat diet or obesity. Overall design: mRNA profiles of 8 weeks wild type (WT) and Trim24-/- mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000
TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.
Specimen part
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