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GSE43221
Mus musculus
24 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Retinoic acid receptors (RARs) , , and heterodimerize with Retinoid X receptors (RXR) , , and and bind the cis-acting response elements known as RAREs to execute the biological functions of retinoic acid during mammalian development. RAR mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells. Furthermore, ablation of RAR enhanced the tumor incidence of Ras transformed keratinocytes and was associated with resistance to retinoid mediated growth arrest and apoptosis.
Publication Title
RARγ is essential for retinoic acid induced chromatin remodeling and transcriptional activation in embryonic stem cells.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Ethanol is a well-known teratogen. While this teratogenic potential is well-characterized clinically, the mechanisms through which ethanol exposure results in developmental defects remain unclear. Here we use the zebrafish model to elucidate eye-specific mechanisms that may underlie ethanol-mediated microphthalmia (reduced eye size), using time-series microarray analysis of gene expression of eye tissues of embryos exposed to 1.5% ethanol vs. untreated embryos. We identified 62 genes differentially expressed in ethanol-treated as compared to control zebrafish eyes from all sampling times over the period of retinal neurogenesis (24-48 hours post-fertilization). Application of the EDGE (extraction of differential gene expression) algorithm identified over 3000 genes differentially expressed over developmental time in ethanol-treated embryo eyes as compared to untreated embryo eyes. These lists included several genes indicating a mis-regulated cellular stress response (heat shock response) due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino (MO) targeting heat shock factor 1 (hsf-1) mRNA resulted in a microphthalmic phenotype, suggesting convergent molecular pathways. Manipulation of the heat shock response by thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. Together these data are consistent with roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure in zebrafish.
Publication Title
Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
Human Peptidoglycan Recognition Proteins (PGRPs) kill bacteria, likely by over-activating stress responses in bacteria. To gain insight into the mechanism of PGRP killing of Escherichia coli and bacterial defense against PGRP killing, gene expression in E. coli treated with a control protein (bovine serum albumin, BSA), human recombinant PGRP (PGLYRP4), gentamicin (aminoglycoside antibiotic), and CCCP (membrane potential decoupler) were compared. Each treatment induced unique and somewhat overlapping pattern of gene expression. PGRP highly increased expression of genes for oxidative and disulfide stress, detoxification and efflux of Cu, As, and Zn, repair of damaged proteins and DNA, methionine and histidine synthesis, energy generation, and Fe-S clusters repair. PGRP also caused marked decrease in the expression of genes for Fe uptake and motility.
Publication Title
Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
Description
The incidence of pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but host susceptibility factors are not fully understood. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium complex (MAC) or Mycobacterium abscessus (MAB) and performed transcriptome sequencing (RNA-Seq) to identify relevant gene expression differences. We used cells from 4 different donors in order to try to obtain generalizable data. The differentiated respiratory epithelial cells in ALI were infected with MAC or MAB at MOI of 100:1 or 1000:1, and RNA-seq was performed at 1 and 3 days after infection. We found downregulation of ciliary genes, including several identified with polymorphisms in previous PNTM cohorts. The cytokine IL-32, the superpathway of cholesterol biosynthesis and downstream targets within the IL-17 signaling pathway were all elevated. The integrin signaling pathway was more upregulated by MAB than MAC infection. Working with primary respiratory epithelial cells infected with nontuberculous mycobacteria at ALI, we identified ciliary function, cholesterol biosynthesis, chemokine production and the IL-17 pathway as major targets of host responses to infection. Some of these pathways may be amenable to therapeutic manipulation. Overall design: 44 strand-specific RNA libraries for high-throughput sequencing were prepared (samples from 4 different donors, 57F, 75M, 69F, and 42F, for each condition) using the TruSeq Stranded mRNA Sample Preparation Kit with 750ng of total RNA according to manufacturer's instructions.
Publication Title
Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This study was undertaken to test the hypothesis that short term exposure (4 hours) to physiologic hyperinsulinemia in normal, healthy subjects without a family history of diabetes would induce a low grade inflammatory response, independently of glycemic status. We performed euglycemic hyperinsulinemic (80 mU/m2/min) clamps in 12 healthy, insulin sensitive subjects with no family history of diabetes followed by biopsies of the vastus lateralis muscle taken basally and after 30 and 240 minutes of insulin infusion. Gene expression profiles were generated using Affymetrix HG-U133A arrays. No probe sets had significantly altered expression at 30 minutes of the insulin clamp, but 121 probe sets (117 upregulated and 4 downregulated) were significantly altered after 240 minutes. Hyperinsulinemia in normal, healthy human subjects increased the mRNAs for a number of inflammatory genes and transcription factors. Microarray and quantitative RT-PCR revealed the upregulation of chemokine, cc motif, ligand 2 (CCL2), CCL8, thrombomodulin (THBD), ras-related associated with diabetes (RRAD), metallothionein (MT), and serum/glucocorticoid regulated kinase (SGK), and downregulation of CITED2 (a CREB-binding protein-interacting transactivator), a known coactivator of PPAR-alpha. Interestingly, SGK and CITED2 are located at chromosome 6q23, where we previously detected strong linkage to hyperinsulinemia. A control saline infusion performed on 3 normal, healthy subjects without a family history of diabetes demonstrated that the genes altered following the euglycemic-hyperinsulinemic clamp were due to insulin and independent of biopsy removal. This study demonstrates that insulin acutely regulates the expression of genes involved in inflammation and transcription, and identifies several candidate genes/pathways for further investigation.
Publication Title
Effect of acute physiological hyperinsulinemia on gene expression in human skeletal muscle in vivo.
Sample Metadata Fields
Sex, Race
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Recent revelations into microRNA function suggest that microRNAs serve as a key player in a robust adaptive response against stress in animals through their fine-tuning capability in gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene mir-60 in the nematode C. elegans promotes adaptive response against oxidative stress; animals lacking mir-60 dramatically extend lifespan under a mild and long-term oxidative stress condition, while they do not increase resistance against a strong and transient oxidative stress exposure. We found that canonical stress responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in the xenobiotic metabolism and pathogen defense response are up-regulated by the mir-60 loss. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. Overall design: To identify genes that respond to the mir-60 loss, RNA expression profiles were examined between the mir-60 loss mutant (mir-60(n4947)) and its control animals using the high-throughput sequencing technology. In this study, we used spe-9(hc88), a temperature-sensitive sterile strain, which has been shown in previous studies to have a lifespan similar to wild-type and widely used in gene expression studies to reduce the effect of RNA contamination from younger progenies. Both spe-9 single and mir-60;spe-9 double mutant animals were cultured at a restrictive temperature 23.5 °C, and treated with paraquat 5 mM during adulthood for chronic oxidative stress. Total RNAs were purified at the following time points: Day 0 young adult for both spe-9 and mir-60;spe-9 (just before paraquat exposure); Day 7 for both spe-9 and mir-60;spe-9 (50% survival time for spe-9); Day 10 for mir-60;spe-9 (50% survival time for mir-60;spe-9). For Day 0 controls, total RNAs were isolated twice independently for biological replicates. cDNA libraries were made for these 7 samples with indexed adapters using TruSeq Stranded mRNA Sample Prep Kit (Illumina), and sequenced on 2 lanes of flow cells on the HiSeq 2000/2500 platform, eventually providing 14 sequencing samples.
Publication Title
An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in <i>C. elegans</i>.
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 2500
Description
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
Publication Title
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
For victims of radiological accidents, rapid dose estimation and damage prediction are essential. Administering the gold-standard biodosimetry chromosome aberration assay requires highly skilled individuals and several days of labor; consequently, rapid turnaround is an important concern. Identification of new dose estimation markers and damage-predicting in vivo molecules to replace the chromosome aberration assay is crucial to improving the delivery time of medical treatment. Here, we investigated the applicability of mRNA levels using a mouse model. Female C57BL/6J mice were X-ray irradiated at various doses, and a DNA microarray was then performed to identify differentially expressed mRNAs in whole blood. The microarray analysis identified 14 radioresponsive mRNAs with more than fourfold differences by pattern matching in the expression at 24 h postirradiation. In particular, mRNA expression of Slfn4, Itgb5, Smim3, Tmem40, Litaf, Gp1bb and Cxx1c was significantly increased in a radiation-dose-dependent manner, as validated by reverse transcription quantitative polymerase chain reaction. We also performed an analysis using the cBioPortal for Cancer Genomics and found that the overall survival of ovarian adenocarcinoma patients with alterations in Smim3 and that of thymoma patients with alterations in Cxx1c had a worse prognosis than patients without these alterations. These findings suggest that the expression of several genes in whole blood was a sensitive and specific biomarker of radiation exposure and can be used as a rapid and reliable prospective molecular biomarker in radiological emergencies.
Publication Title
Identification of Radiation-Dose-Dependent Expressive Genes in Individuals Exposed to External Ionizing Radiation.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Microarray analysis has been applied to the study of ALS in order to investigate gene expression in whole spinal cord homogenates of SOD1 G93A mice and human ALS cases, although the massive presence of glial cells and inflammatory factors has made it difficult to define which gene expression changes were motor neuron specific. Recently, laser capture microdissection (LCM), combined with microarray analysis, has allowed the identification of motor neuron specific changes in gene expression in human ALS cases.
Publication Title
Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed mRNA-seq from hand-dissected fat body tissue from 68hr (after egg laying, AEL) and 92hr AEL Drosophila melanogaster larvae. Fat body was dissected from wild-type (OrR) males and testes were removed. We examined gene expression genome-wide with particular focus on genes in the underreplicated regions in the fat body. Overall design: Sequencing of poly-A selected RNA from 68hr AEL and 92hr AEL wild-type (OrR) Drosophila melanogaster male larvae. Sequences analyzed by Illumina sequencing. Two biological replicates are included for each developmental sample.
Publication Title
Dynamic changes in ORC localization and replication fork progression during tissue differentiation.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples