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Caenorhabditis elegans
30 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants.
Publication Title
Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Illumina HiSeq 1500
Description
Differentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia. Overall design: We analyzed CD45.2+ Lin- Mac+/low Sca1+ cKit+ (LSK) cells from Smarcd2 wild-type, heterozygous and mutant foetal livers in at least 5 replicates Additionally, we analysed three different progenitor populations from Smarcd2 wild-type and homozygous knock-out foetal livers: CD45+Lin-Sca-1-CD177+CD34lowCD16/32 (FCGR)low(MEP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)int (CMP) CD45+Lin-Sca-1-CD177+CD34+CD16/32(FCGR)high (GMP)
Publication Title
Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glioma CIMP (G-CIMP) is a powerful determinant of tumor pathogenicity but the molecular cause of G-CIMP is a fundamental question that is unresolved. Here, we show that mutation of a single gene, isocitrate dehydrogenase 1 (IDH1), directly causes the G-CIMP in gliomas by remodeling the methylome.
Publication Title
IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype.
Sample Metadata Fields
Specimen part
View Samples
GSE76943- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Expression data from HEK293 cells expressing a doxcycline-inducible RANBP6 shRNA
Publication Title
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer.
Sample Metadata Fields
Treatment
View Samples- Drosophila melanogaster
- 1 Downloadable Sample
- Illumina HiSeq 2000
Description
Neuroendocrine (NE) cells use large dense core vesicles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secretory pathway. The DIMM basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two independent genome-wide analyses of DIMM's activities: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to characterize their transcriptional profile. By this combined approach, we showed that DIMM binds to conserved E-boxes in enhancers of 212 genes whose expression is enriched in DIMM-expressing NE cells. DIMM binds preferentially to certain E-boxes within first introns of specific gene isoforms. Statistical machine learning revealed that flanking regions of putative DIMM binding sites contribute to its DNA binding specificity. DIMM's transcriptional repertoire features at least 20 LDCV constituents. In addition, DIMM notably targets the pro-secretory transcription factor, CREB-A, but significantly, DIMM does not target any neuropeptide genes. DIMM therefore prescribes the scale of secretory activity in NE neurons, by a systematic control of the regulated secretory pathway at steps that are both proximal and distal.
Publication Title
Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the basal-like disease subtype and poor prognosis. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of basal-like human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer.
Publication Title
18F-fluorodeoxy-glucose positron emission tomography marks MYC-overexpressing human basal-like breast cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Employing microarray assays, a total of 267 genes were identified that were significantly up- or downregulated in PBMCs of WT-NOD2 patients, compared to healthy donors after challenge with vitamin D (+/-D) and/or a combination (+/-LP) of LPS (lipopolysaccharide) and PGN (peptidoglycan) (p < 0.05; threshold: 2-fold change). For further analysis by real-time PCR, 12 genes with known impact on inflammation and immunity were selected that fulfilled predefined expression criteria. In a larger cohort of patients and controls, a disease-associated expression pattern, with higher transcript levels in vitamin D-treated PBMCs from 5 patients, was observed for three of these genes, CLEC5A (p < 0.030), lysozyme (LYZ; p < 0.047) and TREM1 (p < 0.023). Six genes were found to be expressed in a NOD2- dependent manner (CD101, p < 0.002; CLEC5A, p < 0.020; CXCL5, p < 0.009; IL-24, p < 0.044; ITGB2, p < 0.041; LYZ, p < 0.042). Interestingly, the highest transcript levels were observed in patients with heterozygous NOD2 mutations.
Publication Title
<i>NOD2</i>- and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn's disease patients.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The recent discovery of mutations in metabolic enzymes has rekindled interest in harnessing the altered metabolism of cancer cells for cancer therapy. One potential drug target is isocitrate dehydrogenase 1 (IDH1) which is mutated in multiple human cancers. Here, we examine the role of mutant IDH1 in fully transformed cells with endogenous IDH1 mutations. A selective R132H-IDH1 inhibitor (AGI-5198) identified through a high-throughput screen dose-dependently blocked the ability of the mutant enzyme (mIDH1) to produce R-2-hydroxyglutarate (R-2HG). Under conditions of near complete R-2HG inhibition, the mIDH1 inhibitor induced demethylation of histone H3K9M3 and expression of genes associated with gliogenic differentiation. Blockade of mIDH1 impaired the growth of IDH1-mutant - but not IDH1-wildtype glioma cells without appreciable changes in genome wide DNA methylation. These data suggest that mIDH1 may promote glioma growth through mechanisms beyond its well-characterized epigenetic effects.
Publication Title
An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples