Filters
Technology
Platform
GSE14555
Homo sapiens, Rattus norvegicus
61 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a), Affymetrix Human Genome U133A Array (hgu133a)
Description
(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans.
Publication Title
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Yeast transcription factor Yap1 mediates adaptive response against H2O2 and the cystein thiol reactive Michael acceptor, N-ethylmaleimid (NEM) and acrolein. The response against H2O2 was found to be distinct from that against NEM and acrolein.
Publication Title
Yap1 activation by H2O2 or thiol-reactive chemicals elicits distinct adaptive gene responses.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Chronic exposure of Sprague-Dawley (SD) rats to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Aroclor 1254 results in female-selective induction of hepatic tumors. The relative potency of dioxins and PCB mixtures, such as Aroclor 1254, is often estimated using the internationally endorsed toxic equivalency (TEQ) approach. Comparing the genome wide changes in gene expression in both genders following exposure to toxic equivalent doses of these chemicals should identify critical sets of early response genes while further defining the concept of the TEQ of halogenated aromatic hydrocarbons. Aroclor 1254 at 0.6, 6.0 and 60 mg/kg body weight and TEQ doses of TCDD (0.3 and 3.0 g/kg), calculated to match the top two Aroclor 1254 doses, were orally administered to SD rats for three consecutive days. Day 4 gene expression in hepatic tissue was determined using microarrays. A linear mixed-effects statistical model was developed to analyze the data in relation to treatment, gender, and gender*treatment (G*T) interactions. The genes most changed included 54 genes with and 51 genes without a significant model G*T term. The known aryl hydrocarbon receptor (AHR) battery genes (Cyp1a1, Cyp1a2, Cyp1b1, Aldh3a1), and novel genes, responded in a TEQ dose-dependent manner in both genders. However, an important observation was the apparent disruption of sexually dimorphic basal gene expression, particularly for female rats. Since many of these genes are involved in steroid metabolism, exposure to either TCDD or Aroclor 1254 could disrupt proliferative signals more in female rats as a possible consequence of altered estrogen metabolism. This study extends the findings of previous rodent bioassays by identifying groups of genes, other than the well-characterized AHR response genes, whose disruption may be important in the tumorigenic mechanism in this rat strain.
Publication Title
Toxicogenomic analysis of gender, chemical, and dose effects in livers of TCDD- or aroclor 1254-exposed rats using a multifactor linear model.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G15 coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr, and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Further, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Publication Title
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Test compound one, 5,6-benzoflavone (BNF), was known to act through both the Ah receptor and Nrf2 receptor pathways, while test compounds two and three, 3H-1,2-dithiole-3-thione (D3T) and 4-methyl-5-pyrazinyl-3H-1,2-dithiole-3-thione (OLT), were known to act through the Nrf2 receptor pathway. Furthermore, D3T is known to be more potent and efficacious than OLT for Nrf2 activation. OLT has been shown to exhibit 20-50% of the efficacy of D3T for inhibition of alfatoxin-induced heptic foci. Nonetheless, because OLT is an approved drug, it is currently being evaluated in human phase II intervention trials of biomarkers of alfatoxin-related hepatocellular carcinoma. More recently, BNF was shown to be an effective chemopreventive agent in the rat mammary carcinogen model, inhibiting 7,12-dimethylbenz(a)anthracene DNA adduct formation in liver and mammary cells by 96 and 83% respectively.
Publication Title
Analyzing microarray data with transitive directed acyclic graphs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The estrogen-dependence of breast cancer has long been recognized, however, the role of 17-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that
Publication Title
Epithelial to mesenchymal transition in human breast epithelial cells transformed by 17beta-estradiol.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Combining genome-wide microarray and functional analyses, we found that EGFR activation abrogates barrier function, increasing transepidermal water loss (TEWL) and transepithelial permeability of water-soluble ions and higher molecular weight dextrans, in part by disrupting the expression of tight junction proteins. EGF decreases certain lipid matrix free fatty acids and ceramides by its actions to repress the expression of specific biosynthetic enzymes.
Publication Title
EGFR regulation of epidermal barrier function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 127 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 4000, MinION
Description
The goal of this study was to isolate individual cochlear hair cells and supporting cells from wild type animals in order to characterize the transcriptome of functionally mature auditory hair cells in the mammalian cochlea. Overall design: Single-cell RNA sequencing is a powerful tool by which to characterize the transcriptional profile of low-abundance cell types, however its application to the inner ear has been hampered by the bony labyrinth, tissue sparsity and difficulties in dissociating the ultra-rare cells of the membranous cochlea. Herein, we present a method to isolate individual inner hair cells (IHCs), outer hair cells (OHCs) and Deiters' cells (DCs) from the murine cochlea at any post-natal time point. We isolated of 132 single cells from OHC, IHC, and DC cell types at postnatal day 15 (p15) and performed RNA-Sequencing of these cells using smartseq2 and Illumina HiSeq. An additional 12 single OHCs from the same timepoint were isolated and sequenced using smartseq2 and the Nanopore MinION 1D reads. We leverage single-cell RNA sequencing to analyze these three cell types and generate a multidimensional overview of their transcriptomes. The data provide new insights into OHC motility and the architecture of gene products implicated in hereditary hearing loss. This refined view of transcription in the organ of Corti will enhance to our understanding of the biology of hearing and deafness.
Publication Title
Insights into the Biology of Hearing and Deafness Revealed by Single-Cell RNA Sequencing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissues present within a developing organ remains unclear. Here we use bioengineered “microfluidic chest cavities” to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis and regulates the frequency of airway smooth muscle contraction. Next-generation sequencing analysis shows that lungs held at higher pressure are more mature than lungs held at lower pressure. Timelapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between tissues to control the rate of development of the embryonic lung. Overall design: (i) embryonic mouse lungs at E12.5 were cultured under low or high pressure for 48 hours prior to RNA extraction or (ii) embryonic mouse lungs were isolated from pregnant mice at E12.5, E13.5 and E14.5 prior to RNA extraction
Publication Title
Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.
Sample Metadata Fields
Cell line, Subject
View Samples