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GSE43685
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Maternal obesity during pregnancy leads to a pro-inflammatory milieu in the placenta. We conducted a global transcriptomic profiling in BeWo cells following palmitic acid (PA, 500 uM) and/or TNF-alpha (10 ng/ml) treatment for 24 h. Microarray analysis revealed that placental cytotrophoblasts increased expression of genes related to inflammation, stress response and immediate-early factors in response to plamitic acid, TNF-alpha or a combination of both. Our results suggest that fatty acids and inflammatory cytokines induce inflammation in placental cells via activation of JNK-Egr-1 signaling.
Publication Title
Early growth response protein-1 mediates lipotoxicity-associated placental inflammation: role in maternal obesity.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oxidative stress in adipose tissue and liver has been linked to the development of obesity. NADPH oxidases (NOX) enzymes are a major source of reactive oxygen species (ROS). The current study was designed to determine if NOX2-generated ROS play a role in development of obesity and metabolic syndrome after high fat feeding. Wild type (WT) mice and mice lacking the cytosolic NOX2 activated protein p47phox (P47KO) were fed AIN-93G diets or high fat diets (HFD) containing 45% fat and 0.5% cholesterol for 13 weeks from weaning. Affymetrix array analysis revealed dramatically less expression of mRNA of genes linked to energy metabolism, adipocyte differentiation (PPAR, Runx2) and fatty acid uptake (CD36, lipoprotein lipase) in fat pads from female HFD-P47KO mice compared to HFD-WT females. These data suggest that NOX2 is an important regulator of metabolic homeostasis and that NOX2-associated ROS plays an important role in development of diet-induced obesity particularly in the female
Publication Title
Female mice lacking p47phox have altered adipose tissue gene expression and are protected against high fat-induced obesity.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Beta-arrestin 1 (ARRB1) has been implicated in transcriptional regulation as part of protein complexes bound to chromatin. Here we investigate its effect on transcription and its potential impact on prostate cancer. We report the first genome-wide mapping of chromatin binding for ARRB1 and combine it with expression array data to define its transcriptome. We identify Hypoxia Inducible Factor 1A (HIF1A) as a nuclear binding partner that recruits ARRB1 to promoter regions of HIF1A targets. We show that ARRB1 modulates HIF1A-dependent transcription and promotes a shift in cellular metabolism from oxidative phosphorylation to aerobic glycolysis. In addition, we show that ARRB1 plays an important role in neoplastic transformation, cell growth and resistance to hypoxic stress. This is the first example of an endocytic adaptor protein regulating metabolic pathways and implicates ARRB1 as a tumour promoter.
Publication Title
Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse two-cell stage embryos
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse oocytes
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
T4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
Publication Title
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Publication Title
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples