The transcriptomic changes induced in the human liver cell line HepG2 by 100M menadione, 200M TBH or 50M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.
Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesUnderstanding toxicity pathways of engineered nanomaterials (ENM) has recently been brought forward as a key step in 21st century ENM risk assessment. Molecular mechanisms linked to phenotypic end points is a step towards the development of toxicity tests based on key events, which may allow for grouping of ENM according to their mechanisms of action. This study identified molecular mechanisms underlying mitochondrial dysfunction in human bronchial epithelial BEAS 2B cells following exposure to one of the most studied multi-walled carbon nanotubes (MWCNTs; Mitsui-7). Asbestos was used as a positive control and a non-carcinogenic glass wool material was included as a negative fibre control. Decreased mitochondrial membrane potential (MMP) was observed for MWCNTs at a biologically relevant dose (0.25 g/cm2) and for asbestos at 2 g/cm2, but not for glass wool. Extensive temporal transcriptomic and microRNA expression analyses identified a 330-gene signature related to MWCNT- and asbestos-induced MMP. Fourty-nine of the MMP-associated genes showed highly similar expression patterns over time (six time points) and the majority was found to be regulated by two transcription factors strongly involved in mitochondrial homeostasis, APP and NRF1. In addition, four miRNAs were associated with MMP and one of them, miR-1275, was found to negatively correlate with a large part of the MMP-associated genes. Cellular processes such as gluconeogenesis, glucose metabolism, mitochondrial LC-fatty acid -oxidation and spindle microtubule function were enriched among the MMP-associated genes and miRNAs. These results are expected to be useful in the identification of key events in ENM-related toxicity pathways for the development of molecular screening techniques.
Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells.
Specimen part, Treatment
View SamplesWe analyzed the generation of mouse gliomas following the overexpression of PDGF-B in embryonic neural progenitors. Comparison of our microarray data, with published gene expression data sets for many different murine neural cell types, revealed a closest relationship between our tumor cells and oligodendrocyte progenitor cells, confirming definitively that PDGF-B-induced gliomas are pure oligodendrogliomas.
PDGF-B induces a homogeneous class of oligodendrogliomas from embryonic neural progenitors.
No sample metadata fields
View SamplesAging improves pancreatic ß-cell function in mice. This is a surprising finding since aging is typically associated with functional decline. We performed single-cell RNA sequencing of ß-cells from 3 and 26 month old mice to explore how changes in gene expression contribute to improved function with age. The old mice were healthy, had reduced blood glucose levels and increased ß-cell mass, which correlated to their body weight. ß-cells from young and old mice had similar transcriptome profiles. In fact, only 193 genes (0.89% of all detected genes) were significantly regulated (= 2-fold; false discovery rate < 0.01; normalized counts > 5). Of these, 183 were downregulated and mainly associated with pathways regulating gene expression, cell cycle, cell death and survival as well as cellular movement, function and maintenance. Collectively, our data show that ß-cells from very old mice have transcriptome profiles similar to those of young mice. These data support previous findings that aging is not associated with reduced ß-cell mass or functional ß-cell decline in mice. Overall design: Single-cell RNA sequencing of mouse pancreatic islet beta cells
Single-Cell RNAseq Reveals That Pancreatic β-Cells From Very Old Male Mice Have a Young Gene Signature.
Sex, Age, Specimen part, Subject
View SamplesThis study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells allowing identification of 341 islet cells with high-quality gene expression profiles. The cells clustered into populations of alpha-cells (5%), beta-cells (92%), delta-cells (1%) and PP-cells (2%). We identified cell-type specific transcription factors and pathways primarily involved in nutrient sensing and oxidation and cell signaling. Unexpectedly, 281 cells had to be removed from the analysis due to low viability (23%), low sequencing quality (13%) or contamination resulting in the detection of more than one islet hormone (64%). Collectively, we provide a resource for identification of high-quality gene expression datasets to help expand insights into genes and pathways characterizing islet cell types. We reveal limitations in the C1 Fluidigm cell capture process resulting in contaminated cells with altered gene expression patterns. This calls for caution when interpreting single-cell transcriptomics data using the C1 Fluidigm system. Overall design: Single-cell RNA sequencing of mouse C57BL/6 pancreatic islet cells
Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells.
Specimen part, Cell line, Subject
View SamplesOchratoxin A gene expression profiling in liver and kidney, with time points of exposure from 7 days to 12 motnhs
A toxicogenomics approach to identify new plausible epigenetic mechanisms of ochratoxin a carcinogenicity in rat.
No sample metadata fields
View SamplesGlucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids, and compensatory glucagon hypersecretion involving expansion of pancreatic a-cell mass. Regulation of pancreatic a- and ß-cell growth has drawn a lot of attention because of potential therapeutic implications. Recent findings indicate that hyperaminoacidemia triggers pancreatic a-cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative a-cells, and that Slc38a5 is critical for the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased a-cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino acid-dependent regulation of pancreatic a-cell mass in mice. Overall design: Examination of the transcriptomes of pancreatic islets of mice treated with GCGR-antibody and an isotype control antibody.
Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.
Specimen part, Cell line, Subject
View SamplesGlucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids and compensatory glucagon hypersecretion involving expansion of pancreatic a cell mass. Recent findings indicate that hyperaminoacidemia triggers pancreatic a cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative a cells and that Slc38a5 controls the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased a cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino-acid-dependent regulation of pancreatic a cell mass in mice. Overall design: Examination of the transcriptomes of islet non-beta-cells of GcgR knock out mice.
Amino Acid Transporter Slc38a5 Controls Glucagon Receptor Inhibition-Induced Pancreatic α Cell Hyperplasia in Mice.
Sex, Specimen part, Cell line, Subject
View SamplesIdentifying novel candidate biomarker gene differentially expressed in the peripheral blood cells of patients with early stage acute myocardial infarction using microarray as a high throughput screening technology.
Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome.
Specimen part, Disease, Time
View Samples