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GSE98321
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Abhd15 is mainly expressed in white adipose tissues and highly upregulated upon adipogenesis. Abhd15 expression is correlated with insulin resistance in obese humans, however its physiological function remains unknown. We used the microarray technology to gain insight into ABHD15s physiological function by identifying dysregulated genes in eWAT from Abhd15-ko mice in comparison to WT mice.
Publication Title
Loss of ABHD15 Impairs the Anti-lipolytic Action of Insulin by Altering PDE3B Stability and Contributes to Insulin Resistance.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Identfification of MEF2A target genes using ChIP-exo and RNA-seq in skeletal muscle and primary cardiomyocytes. MEF2 plays a profound role in the regulation of transcription in cardiac and skeletal muscle lineages. To define the overlapping and unique MEF2A genomic targets, we utilized ChIP-exo analysis of cardiomyocytes and skeletal myoblasts. Of the 2783 and 1648 MEF2A binding peaks in skeletal myoblasts and cardiomyocytes, respectively, 294 common binding sites were identified. Genomic targets were compared to differentially expressed genes in RNA-seq analysis of MEF2A depleted myogenic cells. Overall design: The effect of MEF2A gene silencing on gene expression in myoblasts was assessed at 48 hr DM. Up and downregulated genes were then compared to MEF2A target genes identified in ChIP-exo analysis of 48 hr DM C2C12 myoblasts cells and primary cardiomyocytes.
Publication Title
Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HNF4alpha is a master regulator of hepatic differentiation. In this study, HNF4alpha was deleted in adult mice using a Cre-LoxP system where Cre recombinase was delivered using an AAV8 virus.
Publication Title
Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
Publication Title
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- NextSeq 500
Description
Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. We screened several MRT cell lines each with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Using two compounds currently in clinical development, idasanutlin and ATSP-7041, we show that MRT cells are more sensitive than other p53 wild-type cancer cell lines to MDM2 and dual MDM2/4 inhibition in vitro. These compounds cause significant upregulation of the p53 pathway in MRT cells, and sensitivity is ablated by CRISPR-Cas9-mediated inactivation of TP53. We show that loss of SMARCB1, a subunit of the SWI/SNF (BAF) complex mutated in nearly all MRT, sensitizes cells to MDM2 and MDM2/4 inhibition by enhancing p53-mediated apoptosis. Both MDM2 and MDM2/4 inhibition slowed MRT xenograft growth in vivo, with a five-day idasanutlin pulse causing marked regression of all xenografts including durable complete responses in 50% of mice. Together, these studies identify a genetic connection between mutations in the SWI/SNF chromatin-remodeling complex and the tumor suppressor gene p53, and provide preclinical evidence to support the targeting of MDM2 and MDM4 in this often-fatal pediatric cancer. Overall design: RNA-seq in TTC642 MRT cells treated with idasanutlin compared to DMSO
Publication Title
MDM2 and MDM4 Are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oncogene-induced senescence (OIS), a terminal cell cycle block countering (pre)neoplastic lesions, is characterised on the molecular level by trimethylated histone H3 lysine 9 (h3K9me3), a transcriptionally repressive chromatin mark linked to silencing of S-phase-promoting genes. Whether H3K9-governed chromatin remodelling influences anticancer treatment-induced senescence (TIS) and whether functional control of this mark impacts on treatment outcome is not known. We used global gene expression profiling by microarrays to gain insight into the molecular responses of Emu-myc; Suv39h1-/- B-cell lymphoma cells to senescence-inducing anticancer agent Adriamycin (ADR).
Publication Title
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hematopoietic stem and progenitor cells (HPCs) can be maintained in vitro, but the vast majority of their progeny loses stemness during culture. We have analyzed DNA methylation (DNAm) profiles of freshly isolated CD34+ cells and upon expansion on either tissue culture plastic (TCP) or mesenchymal stromal cells (MSCs). Cultured HPCs acquired significant DNA-hypermethylation, particularly in up-stream promoter regions and shore-regions of CpG islands (CGIs). To analyze if these DNAm changes are relevant for differential gene expression we analyzed gene expression profiles of additional samples. As expected highly expressed genes (10% with highest signal intensity in gene expression arrays) were hardly methylated at promoter regions, CGIs and shore-regions.
Publication Title
Hematopoietic stem and progenitor cells acquire distinct DNA-hypermethylation during in vitro culture.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Stabilized Alpha-Helix peptides of BCL9 HD2 (SAH-BCL9) block BCL9 and B9L interactions with beta-catenin and specifically downregulate Wnt target gene expression.
Publication Title
Targeted disruption of the BCL9/β-catenin complex inhibits oncogenic Wnt signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 1 Downloadable Sample
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Zinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Publication Title
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
Sample Metadata Fields
No sample metadata fields
View Samples