Filters
Technology
Platform
GSE62868
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Genome-wide association studies in human type 2 diabetes (T2D) have renewed interest in the pancreatic islet as a major site of T2D risk. In this study, microarray data collected from mouse islets were used to identify genes that are regulated by cytokines at levels consistent with the chronic low-grade inflammation observed in T2D. The most cytokine-sensitive genes were then examined for association of single nucleotide polymorphisms (SNPs) with acute insulin response to glucose (AIRg) measured in the Genetics UndeRlying DIAbetes in HispaNics (GUARDIAN) study. In GUARDIAN, there was evidence of association of AIRg with SNPs in ARAP3 (5q31.3), F13A1 (6p25.3), KLHL6 (3q27.1), NID1 (1q42.3), PAMR1 (11p13), RIPK2 (8q21.3), and STEAP4 (7q21.12). These data support the mouse islet microarray data in detection of seven novel genes with potential importance to islet dysfunction in T2D. To further assess each gene, murine islets were exposed for 48-hrs to the following stressors representing models of beta-cell failure: 20nM rotenone (oxidative stress), 100nM thapsigargin (ER stress), 10pg/ml IL-1B + 20pg/ml IL-6 (cytokines/low-grade inflammation), 28mM glucose (hyperglycemia), or 50uM palmitate + 100uM oleate + 50uM linoleate (lipotoxicity). RT-PCR revealed that F13a1 was downregulated 3.3-fold by cytokines (P<0.05) and 2.6-fold by rotenone (P<0.05), Klhl6 was upregulated 4.3-fold by thapsigargin (P<0.01), Ripk2 was mildly (1.5-3-fold) but significantly upregulated by all stressors (P<0.05), and STEAP4 was profoundly cytokine-sensitive (167-fold upregulation, P<0.01). These findings reveal promising leads in elucidating islet dysfunction during the development of T2D.
Publication Title
An Islet-Targeted Genome-Wide Association Scan Identifies Novel Genes Implicated in Cytokine-Mediated Islet Stress in Type 2 Diabetes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analyses of memory CDKN2A-/- CD8 T lymphocytes expressing an active form of the transcription factor Stat5.
Publication Title
Control of CD8 T cell proliferation and terminal differentiation by active STAT5 and CDKN2A/CDKN2B.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To understand how an inhibition of the mitochondrial ATP synthase affects transcriptional programming and to identify potential candidates of the signaling machinery involved in ATP synthase deficiency responses, we used oligomycin on seedling liquid cultures. Seedlings were harvested at time points 0, 1 and 4 h after the start of oligomycin and control (EtOH) treatments. Already 1 h after addition of oligomycin a total of 102 genes were more than threefold up-regulated and 14 genes were repressed, with most of them showing persistent changes. After 4 h, 580 additional genes were more than threefold up-regulated, and 152 genes were repressed by oligomycin. Several genes for alternative NAD(P)H dehydrogenases and alternative oxidases (AOX1a, AOX1d and NDA1) were up-regulated early, and additional homologs (NDA2, NDB2, NDB4 and AOX1b) followed 4 h after the start of treatment. Several genes for subunits of complex I, complex IV and the ATP synthase were induced whereas hardly any genes encoding enzymes of glycolysis and the TCA cycle changed. Additionally, four of five hallmark genes for oxidative stress were increased by oligomycin. These genes are At2g21640 (UPOX), At1g19020, At1g05340 and At1g57630 and code for proteins of unknown function. Among oxidative stress proteins with known functions, several H2O2-responsive Glutathione-S-transferases and BCS1 (CYTOCHROME BC1 SYNTHESIS) were strongly up-regulated already after 1 h. BCS1 is induced by salicylic acid and independent of other reactive oxygen signaling (ROS) pathways, such as H2O2. The results indicate that several different ROS and defense signaling pathways were induced simultaneously by oligomycin. This is further corroborated by induction of several transcription factors of the WRKY and NAC families, which have been previously implicated in coordinating cellular defense signaling.
Publication Title
Downregulation of the δ-subunit reduces mitochondrial ATP synthase levels, alters respiration, and restricts growth and gametophyte development in Arabidopsis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The biological effects of TTR proteins in the vasculature remain unknown.
Publication Title
Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 43 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
gene expression profiling in different zones along the gradient of the growing maize leaf balde aover a time course of dirunal cycle and carbon starvation by extension of the night
Publication Title
The Interplay between Carbon Availability and Growth in Different Zones of the Growing Maize Leaf.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
In our efforts to evaluate the function of the IL-8 receptor CXCR2 in Acute Lymphoblastic Leukemia (ALL) cells, we made use of SB225002 (N-(2-hydroxy-4-nitrophenyl)-N-(2-bromophenyl)urea), a drug initially described as a CXCR2 antagonist. Although the CXCR2 receptor was found to be non-functional in ALL, B- and T-ALL cell lines were sensitive to SB225002.
Publication Title
SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study, we jointly profiled mRNA and miRNA expression to determine the role of miRNAs in AD, and whether the levels of miRNAs are related to those of target mRNAs. We found a bias towards positive correlation between levels of miRNAs and those of their targets.
Publication Title
Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 44 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 115 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
Publication Title
Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Time
View Samples