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GSE54976
Mus musculus
17 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The HMG-box factor Tcf1 is required during T-cell development in the thymus and mediates the nuclear response to Wnt signals. Tcf1/ mice have previously been characterized and show developmental blocks at the CD4CD8 double negative (DN) to CD4+CD8+ double positive transition. Due to the blocks in T-cell development, Tcf1/ mice normally have a very small thymus. Unexpectedly, a large proportion of Tcf1/ mice spontaneously develop thymic lymphomas with 50% of mice developing a thymic lymphoma/leukemia at the age of 16 wk. These lymphomas are clonal, highly metastatic, and paradoxically show high Wnt signaling when crossed with Wnt reporter mice and have high expression of Wnt target genes Lef1 and Axin2. In wild-type thymocytes, Tcf1 is higher expressed than Lef1, with a predominance of Wnt inhibitory isoforms. Loss of Tcf1 as repressor of Lef1 leads to high Wnt activity and is the initiating event in lymphoma development, which is exacerbated by activating Notch1 mutations. Thus, Notch1 and loss of Tcf1 functionally act as collaborating oncogenic events. Tcf1 deficiency predisposes to the development of thymic lymphomas by ectopic up-regulation of Lef1 due to lack of Tcf1 repressive isoforms and frequently by cooperating activating mutations in Notch1. Tcf1 therefore functions as a T-cellspecific tumor suppressor gene, besides its established role as a Wnt responsive transcription factor. Thus, Tcf1 acts as a molecular switch between proliferative and repressive signals during T-lymphocyte development in the thymus.
Publication Title
The nuclear effector of Wnt-signaling, Tcf1, functions as a T-cell-specific tumor suppressor for development of lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. We tested the hypothesis that MNO, but not MAO, people are protected from the adverse metabolic effects of weight gain. To this end, global transcriptional profile in adipose tissue before and after weight gain was evaluated by microarray analyses.
Publication Title
Metabolically normal obese people are protected from adverse effects following weight gain.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
The Epidermal Growth Factor Receptor (EGFR) regulates a diverse set of biological processes including cell growth, proliferation, and differentiation. Deregulation of the EGFR pathway has been implicated in a variety of human diseases including cancer. Gefitinib and erlotinib are tyrosine kinase inhibitors (TKIs) that have demonstrated clinical benefit for patients with Non-small cell lung cancer (NSCLC) and EGFR activating mutations. However, patients invariably acquire resistance to TKI treatment through a number of mechanisms. We utilized in vitro models of NSCLC with EGFR activating mutations and derived three isogenic cell lines with acquired resistance to gefitinib. We next studied genomewide mRNA expression in resistance and wild type cells and their effect in the reprogramming of pathways in lung cancer cell line models.. Overall design: Differntial expresssion profile of transcripts of parental (HCC827) and EGFR-TKI (HCC827 ZDR3) resistance cells
Publication Title
JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-mutant NSCLC Cell Lines.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Pressure overload (PO) leads first to cardiac hypertrophy and later to heart failure. In mice, PO leads to sex differences in cardiac morphology and function. However, early sex differences in gene regulation that precede sex differences in function have not yet been identified.
Publication Title
Sex-specific pathways in early cardiac response to pressure overload in mice.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The association of DNA CpG methylation (or its absence) with occupancy of histone post translational modifications has hinted at an underlying crosstalk between histone marks and DNA methylation in patterning the human methylome, an idea supported by corresponding alterations to both histone marks and DNA methylation during malignant transformation. This study investigated the framework by which histone marks influence DNA methylation. Using RNAi in a human pluripotent embryonic carcinoma cell line we depleted essential components of the histone modifying complexes that establish the posttranslational modifications H3K4me3, H3K27me3, and H2AK119ub, and we assayed the impact of the subsequent loss of these marks on the DNA methylome. Absence of H2AK119ub resulted predominantly in hypomethylation across the genome. Removal of H3K4me3 or, surprisingly, H3K27me3 caused CpG island hypermethylation at a subset of loci. Intriguingly, many promoters were co-regulated by all three histone marks, becoming hypermethylated with loss of H3K4me3 or H3K27me3 and becoming hypomethylated with depletion of H2AK119ub, and many of these co-regulated loci were among those that are commonly, aberrantly hypermethylated in cancer.
Publication Title
Impact of human MLL/COMPASS and polycomb complexes on the DNA methylome.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
We have identified the transcription factor forkhead box protein F2 (Foxf2) to be upregulated in its expression during the EMT process and studied its functional contribution to EMT by siRNA-mediated knockdown in NMuMG cells treated for 4 days with TGFbeta followed by mRNA-sequencing. Our analysis revealed a dual role of Foxf2 during TGFbeta-induced EMT in promoting apoptosis while inducing cell junction breakdown and migration. Overall design: mRNA sequencing of NMuMG/E9 cells transfected with control siRNA or Foxf2 specific siRNA and treated with TGFbeta for 4 days
Publication Title
Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by promoting apoptosis yet enabling cell junction dissolution and migration.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nucleosome positioning changes during human embryonic stem cell differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The TET family of dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), but their involvement in establishing normal 5mC patterns during mammalian development and their contributions to aberrant control of 5mC during cellular transformation remains largely unknown. We depleted TET1, TET2, and TET3 by siRNA in a pluripotent embryonic carcinoma cell model and examined the impact on genome-wide 5mC and 5hmC patterns. TET1 depletion yielded widespread reduction of 5hmC, while depletion of TET2 and TET3 reduced 5hmC at a subset of TET1 targets suggesting functional co-dependence. TET2 or TET3-depletion also caused increased 5hmC, suggesting they play a major role in 5hmC removal. All TETs prevent hypermethylation throughout the genome, a finding dramatically illustrated in CpG island shores, where TET depletion resulted in prolific hypermethylation. Surprisingly, TETs also promote methylation, as hypomethylation was associated with 5hmC reduction. TET function was highly specific to chromatin environment: 5hmC maintenance by all TETs occurred at polycomb-marked chromatin and genes expressed at moderate levels; 5hmC removal by TET2 is associated with highly transcribed genes enriched for H3K4me3 and H3K36me3. Importantly, genes prone to hypermethylation in cancer become depleted of 5hmC with TET deficiency, suggesting the TETs normally promote 5hmC at these loci, and all three TETs are required for 5hmC enrichment at enhancers, a condition necessary for expression of adjacent genes. These results provide novel insight into the division of labor among TET proteins and reveal an important connection of TET activity with chromatin landscape and gene expression.
Publication Title
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples