Filters
Technology
Platform
GSE69512
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Msi2 is a critical regulatior of myeoid leukemia, and these data identify genes that are changed following Msi2 deletion in bcCML and de novo AML stem cells.
Publication Title
Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
Purpose: The goals of this study were to identify quantitative gene expression differences between wild type, Musashi1 null, Msuashi2 null and Musashi1/Musashi2 null MIAPaCa2 pancreatic cancer cells Overall design: mRNA profiles of MIA PaCa-2 cancer cells were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.
Publication Title
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentationand profound drug resistance. Here we developed novel fluorescent reporter mice that show that the stem cell determinant, Musashi (Msi) is a critical element of pancreatic cancer progression.
Publication Title
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF.
Publication Title
Tubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Background: The main focus of the work was the evaluation of gene expression differences between our established NSCLC 3D cell culture model and the 2D cell culture in regard to the use of our model for drug screening applications.
Publication Title
3D-cultivation of NSCLC cell lines induce gene expression alterations of key cancer-associated pathways and mimic <i>in-vivo</i> conditions.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
The circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question we performed transcriptomic analysis in mice with inducible and conditional ablation of the circadian clock system in the renal tubular cells (Bmal1lox/lox/Pax8-rtTA/LC1 mice). Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport. In parallel, kidneys from Bmal1lox/lox/Pax8-rtTA/LC1 mice exhibited a significant decrease in the NAD+/NADH ratio suggesting an increased anaerobic glycolysis and/or decreased mitochondrial function. In-depth analysis of two selected pathways revealed (i) a significant increase in plasma urea levels correlating with increased renal arginase 2 (Arg2) activity, hyperargininemia and increase of the kidney arginine content; (ii) a significantly increased plasma creatinine concentration and reduced capacity of the kidney to secrete anionic drugs (furosemide), paralleled by a ~80% decrease in the expression levels of organic anion transporter OAT3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at both the intra-renal and systemic levels and are involved in drug disposition. Overall design: Mice with a specific ablation of the Arntl gene encoding BMAL1 in the renal tubular cells were compared to wild-type littermate at ZT4 and ZT16 (ZT – Zeitgeber time units; ZT0 is the time of light on and ZT12 is the time of light off).
Publication Title
Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Normal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Publication Title
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Dysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with ß-linked N-acetylglucosamine (O- glcnAcylation) via overexpression of the O-glcnAc–regulating enzymes O- glcnAc transferase (OGT) or O- glcnAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O- glcnAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-glcnAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-glcnAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq in SH-SY5Y cells indicated transcriptome reprogramming and down regulation of the NRF2-mediated antioxidant response. Sustained O-glcnAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-glcnAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-glcnAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases. Overall design: SY5Y cells were adapted to long term O-glcnAcase (OGA) inhibition using the specific OGA inhibitor Thiamet-G (tmg) or glucosamine treatment for 3 weeks. After adaptation to the growth conditions, cells were harvest and RNA isolated for Next Generation RNA sequencing. Briefly, cDNA library was prepared using Illumina TruSeq Stranded mRNA sample preparation kit (Illumina) as manufacturer's instruction. Total RNA was isolated using the same method as previously described and 800 ng of the total RNA per reaction was used to initiate the protocol. The quality of RNA sequencing results was first assessed using FastQC (0.11.2). RSEM (1.2.22) was utilized to align the reads to the human reference genome HG38 and to calculate gene expression values. EdgeR (3.14.0) was then used to normalize the expression values using the TMM-method (weighted trimmed mean of M-values), and for differential expression analyses. First, the negative binomial conditional common likelihood was maximized to estimate a common dispersion value across all genes (estimateCommonDisp). Next, tagwise dispersion values were estimated by an empirical Bayes method based on weighted conditional maximum likelihood (estimateTagwiseDisp). Finally, the differentially gene expression was calculated by computing genewise exact tests for differences in the means between two groups of negative-binomially distributed counts. Hierarchical clustering analysis was determined using Euclidean distance. The following R-packages were utilized for calculations and visualizations: plots and edgeR.
Publication Title
Sustained <i>O-</i>GlcNAcylation reprograms mitochondrial function to regulate energy metabolism.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of resting (or surveying) microglia to an activated (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity.
Publication Title
Microglia in ischemic brain injury.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
Goal of this study is to identify annotated and non-annotated genes transcriptionally regulated by small heterodime partner (SHP, Nrob2) expression. Overall design: Liver 5'' capped RNA samples from three SHP -/- and three wild type mice were sequenced with Illumina GAII sequencer.
Publication Title
A Novel Small Molecule Activator of Nuclear Receptor SHP Inhibits HCC Cell Migration via Suppressing Ccl2.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples