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GSE34219
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
M21 or M21L cells were grown either in a 2-dimensional culture (on plastic) or in a 3-dimensional-collagen model.
Publication Title
Protein kinase Cα (PKCα) regulates p53 localization and melanoma cell survival downstream of integrin αv in three-dimensional collagen and in vivo.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Sickle cell disease (SCD) results from a point mutation in the ß-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)–like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell–derived erythroid progenitors. We investigated the ability of dimethyl fumarate (DMF), a small-molecule Nrf2 agonist, to activate ?-globin transcription and enhance HbF in tissue culture, murine and primate models. DMF recruited Nrf2 to the ?-globin promoters and the locus control region of the ß-globin locus in erythroleukemia cells, elevated HbF in SCD donor–derived erythroid progenitors, and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice induced HbF and increased Nrf2-dependent genes to detoxify heme and limit inflammation. This improved hematological parameters, reduced plasma-free Hb, and attenuated inflammatory markers. Chronic DMF administration to nonanemic primates increased ?-globin mRNA in BM and HbF protein in red cells. DMF represents a potential therapy for SCD to induce HbF and augment vasoprotection and heme detoxification Overall design: RNA-Seq of 30 samples
Publication Title
Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and corrects anemia in sickle cell disease.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The aim of this study was to characterize the stroma displayed by different models of breast cancer tumors in mice. For this purpose, transcriptomic and flow cytometry analyses on murine populations were performed in a series of 25 PDXs and 2 most commonly used GEMs (MMTV-PyMT and MMTV-erBb2). Specifically, macrophages from 5 models were sorted and profiled by gene expression and phenotypically characterized by flow cytometry.
Publication Title
Characterization of Breast Cancer Preclinical Models Reveals a Specific Pattern of Macrophage Polarization.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Here we study the adult functions of the single Drosophila member of this subfamily, DHR78, with the goal of defining its ancestral functions in the absence of genetic redundancy. We show that DHR78 mutants have a shortened lifespan and reduced motility. Mated DHR78 mutant females display reduced triglycerides along with a reduced feeding rate. Transcriptional profiling reveals a major role for DHR78 in promoting the expression of genes that are abundantly expressed in the midgut, suggesting that it contributes to nutrient uptake. We also identify roles for DHR78 in maintaining the expression of genes in the ecdysone and Notch signaling pathways. Overall design: Comparison of the transcriptional profile of DHR78-transheterozygote female mutants in a btl>DHR78 background with genetically matched controls
Publication Title
Adult functions for the Drosophila DHR78 nuclear receptor.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Although SIRT1 plays a central role in maintaining metabolic homeostasis, the molecular mechanisms remain unclear. Here we show that loss of the Drosophila SIRT1 homolog sir2 leads to the progressive onset of diabetic phenotypes, similar to studies of SIRT1 in mice. Sir2 function is both necessary and sufficient in the fat body to maintain peripheral insulin sensitivity. This activity is mediated by the Drosophila HNF4 nuclear receptor, which is deacetylated and stabilized through protein interactions with Sir2. This study demonstrates that the key metabolic activities of SIRT1 have been conserved through evolution and establishes HNF4 as a critical downstream target. Overall design: 4 sir2 mutant, 4 control samples, independent biological replicates
Publication Title
Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila.
Sample Metadata Fields
Age, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
There is a good deal of indirect evidence that improved insulin sensitivity may contribute to improved lifespan of mice in which aging has been slowed by mutations, drugs, or dietary means, even in stocks of mice that do not show signs of late-life diabetes. Peripheral responses to insulin can be augmented by over-expression of Syntaxin 4 (Syn4), a membrane SNARE protein. We show here that Syn4 transgenic (Tg) mice live approximately 33% longer than controls, and show increased peripheral insulin sensitivity, even at ages where controls show age-related insulin resistance. Hence, presumably Syn4 Tg mice spend more hours of each day under normoglycemic conditions, which may slow multiple aspects of aging and thereby extend lifespan, even in non-diabetic mice.
Publication Title
Syntaxin 4 Overexpression Ameliorates Effects of Aging and High-Fat Diet on Glucose Control and Extends Lifespan.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Acquired resistance to endocrine therapy occurs with high frequency in patients with luminal breast cancer (LBC). We report here the establishment of four patient-derived xenograft models of LBC with acquired resistance in vivo to tamoxifen and estrogen deprivation.
Publication Title
Acquired resistance to endocrine treatments is associated with tumor-specific molecular changes in patient-derived luminal breast cancer xenografts.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 27 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies genes that alter their expression in synchrony with the late third instar and prepupal pulses of 20E.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
This study identifies those genes that are dependent on EcR for their proper regulation at the onset of metamorphosis in Drosophila melanogaster.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
To identify 20E-regulated genes, wandering third instar larvae were dissected and their organs were cultured in the presence of either no hormone, 20E alone, cycloheximide alone, or 20E plus cycloheximide for six hours.
Publication Title
The genomic response to 20-hydroxyecdysone at the onset of Drosophila metamorphosis.
Sample Metadata Fields
No sample metadata fields
View Samples