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SRP131375
Homo sapiens
160 Downloadable Samples
NextSeq 500
Description
We provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of the polychlorinated biphenyl (PCB) 126, one of the most potent chemical inducing NAFLD. Additionnally, three concentration of the pesticide active ingredient glyphosate were tested. This ultimately suggested sensitive biomarkers of exposure. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. Our study provides grounds for the development of molecular signatures of fatty liver diseases to rapidly assess toxic effects of chemicals in the HepaRG cell line. Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the PCB were then tested from day 8 to day 14, in order to cover a wide range of biological effects, starting from low environmental exposures (100 pM) to high concentrations of (1 uM), with an intermediate concentration (10 nM). Three concentrations of glyphosate, or one concentration of the Roundup herbicide (Grand Travaux +) were also tested in the same system.
Publication Title
Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 44 Downloadable Samples
- NextSeq 500
Description
We provide here the alterations in gene expression profiles of HepaRG cells, a validated model for cellular steatosis, exposed to three concentration of quizalofop-p-ethyl, isoxaflutole and mesotrione Overall design: Differentiated HepaRGTM cells (HPR 116) were purchased from Biopredic International. The cells were kept in the general purpose medium until day 8, when the culture becomes well organized and includes well-delineated trabeculae and many canaliculi-like structures. Three concentrations of the different pesticide active ingredients (quizalofop-p-ethyl, isoxaflutole and mesotrione ) were then tested from day 8 to day 14. In order to ensure coverage of a wide range of potential biological effects, three concentrations of each active principle were tested; a concentration representative of low environmental exposure (0.1 uM), an intermediate concentration (10 uM) and a high concentration (1000 uM).
Publication Title
Comparison of transcriptome responses to glyphosate, isoxaflutole, quizalofop-p-ethyl and mesotrione in the HepaRG cell line.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 120 Downloadable Samples
- NextSeq 500
Description
We provide here the alterations in gene expression profiles of 3T3-L1 cells, a validated model for adipogenesis, exposed to quizalofop-p-ethyl for 6h, 24h and 12 days. Overall design: Exposure to endocrine disrupting chemicals is a risk factor for obesity. The most commonly used pesticide active ingredients have never been tested in an adipogenesis assay. We tested for the first time the lipid accumulation induced by glyphosate, 2,4-dichlorophenoxyacetic acid, dicamba, mesotrione, isoxaflutole and quizalofop-p-ethyl (QpE) in 3T3-L1 adipocytes. Only QpE caused triglyceride accumulation from a concentration of 1 µM. We thus conducted an in-depth investigation of molecular mechanisms responsible for the adipogenic effects of quizalopfop-p-ethyl by an RNA-seq analysis.
Publication Title
Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Angiogenesis is tightly regulated by both soluble growth factors and cellular interactions with the extracellular matrix (ECM). While cell adhesion via integrins has been shown to be required for growth factor signaling and downstream angiogenesis, the effects of quantitative changes in cell adhesion and spreading against the ECM remain less clear.
Publication Title
Decreased cell adhesion promotes angiogenesis in a Pyk2-dependent manner.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although much is known about focal adhesion signaling induced by cell adhesion, how adhesion directs changes in transcription to control cell behavior is far less understood. Here we describe a novel mechanism by which changes in adhesion switch the activities of the mitogen-activated protein kinases (MAPKs) c-Jun N-terminal kinase (JNK) and p38, resulting in the differential activation and promoter occupancy of the SRF cofactors, the ternary complex factors (TCFs) Sap-1 and Net. Adhesion-induced MAPK/TCF switching controls immediate early gene expression and proliferation. This mechanism is of physiological relevance, as proliferative regulation by the TCFs is conserved in an ex ovo model of angiogenesis. Furthermore, microarray analysis identified novel genes and adhesive functions regulated by Sap-1 and Net. Thus our data identify the TCFs as key regulators of adhesion-induced transcription and cell behavior.
Publication Title
Adhesion regulates MAP kinase/ternary complex factor exchange to control a proliferative transcriptional switch.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 69 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
SCA1, a fatal neurodegenerative disorder, is caused by a CAG expansion encoding a polyglutamine stretch in the protein ATXN1. We used RNA-seq to profile cerebellar RNA expression in ATXN1 mice, including lines with ataxia and progressive pathology and lines having ataxia in absence of Purkinje cell progressive pathology. Weighted Gene Coexpression Network Analysis of the cerebellar RNA-seq data revealed two gene networks that significantly correlated with disease, the Magenta (342 genes) and Light Yellow (35 genes) Modules. Features of the Magenta and Light Yellow Modules indicate they reflect distinctive pathways. The Magenta Module provides a description of suppressed transcriptional programs reflecting disease progression in Purkinje cells, while the Lt Yellow Module reflects other transcriptional programs activated in response to disease in Purkinje cells as well as other cerebellar cell types. We also found that up-regulation of cholecystokinin (Cck) blocked progression of Purkinje cell pathology and that loss of Cck function in mice lacking progressive disease enabled Purkinje cell pathology to progress to cell death. Overall design: Cerebellar mRNA expression profiles from ATXN1[82Q], ATXN1[30Q], and ATXN1[30Q]-D776 transgenic mice and wild type/FVB mice at 5 weeks, 12 weeks and 28 weeks of age ---------------------------- cuffnorm_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_genes.fpkm_tracking.txt: CuffNorm normalized values for all samples (snoRNAs and miRNAs removed) cuffdiff_week5_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 5; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week12_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 12; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week28_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 28; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week5_vs_week12_vs_week28_ATXN1.82Q_gene_exp.diff.txt: Cuffdiff comparison between ATXN1[82Q] at week 5, week 12 and week 28 cuffdiff_week5_vs_week12_vs_week28_ATXN1.30Q.D776_gene_exp.diff.txt: Cuffdiff comparison between ATXN1[30Q]D776 at week 5, week 12 and week 28 cuffdiff_week5_vs_week12_vs_week28_FVB_gene_exp.diff.txt: Cuffdiff comparison between wt/FVB at week 5, week 12 and week 28
Publication Title
Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Here we determine the target gene sets controlled by PRMT1 or CSNK1a1 in maintaining the undifferentiated state of primary human keratinocytes.
Publication Title
CSNK1a1 Regulates PRMT1 to Maintain the Progenitor State in Self-Renewing Somatic Tissue.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders.
Publication Title
The disruption of Celf6, a gene identified by translational profiling of serotonergic neurons, results in autism-related behaviors.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 483 Downloadable Samples
- NextSeq 500
Description
Rare heterozygous coding variants in the triggering receptor expressed in myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer''s disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell-type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity. We primarily discovered changes in an endothelial gene-enriched subnetwork at 4 months, including a shift toward a more central role for the amyloid precursor protein gene, coupled with widespread disruption of other cell-type subnetworks, including a subnetwork with neuronal identity. We reveal an unexpected potential role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signaling hub, suggesting an underlying link between immune response and vascular disease in dementia. Methods: We performed differential expression and co-expression network analysis on a RNA-Seq profiled Trem2 knockout (KO) mouse using two brain areas sampled at 4- and 8-months to obtain a systems level view of the effects of the absence of Trem2. Results: The absence of Trem2 has a stronger effect at an earlier age with the number of differential expressed (DE) genes being 17-fold greater at 4 months than at 8 months in cortex. By integrating DE genes and network analysis, we discovered gene clusters associated with the disruption of blood vessel formation at 4 months of age and protein targeting primarily affecting the hippocampus at 8 months. Further integration of cell type and ontology information revealed a large disruption of a gene module enriched for endothelial cell markers coinciding with the module enriched for neuron cell markers having weaker connections to modules with oligodendrocyte and astrocyte identities. The module with neuronal identity has decreased expression only in the KO where it has closer association with a new module enriched for phagocytic functions. Conclusions: Combining gene co-expression and differential expression analysis on a newly generated RNA-Seq profiled Trem2 KO mouse demonstrate that the absence of Trem2 produces a disruption which mainly affects endothelialon related processes at 4 months of age. It results in a ripple effect that disrupts the cross-talk of other cell types at 8 months, including reduced expression of a gene module enriched in neuron related functions and a shift towards a more central role for App. This study reveals an unexpected role of Trem2 in the homeostasis of endothelial cells that goes beyond its known functions as a microglial receptor and signaling hub suggesting new paths for investigation at the intersection between Trem2, Alzheimer's disease and vascular dementia. Overall design: Hippocampus and cortex were selected because they represent tissues affected in AD at early and late stages, respectively (Matarin 2015, Mastrangelo 2008). Brain tissue samples were obtained from male Trem2 knockout (KO) and wild type (WT) control mice at two time points: 4 months and 8 months. These time points span the onset and late disease stages in well established AD mouse models (Matarin 2015). RNA-Seq was used to profile the transcriptomes for each sample. Two technical replicates were obtained for each sample.
Publication Title
Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples