Filters
Technology
Platform
SRP167078
Mus musculus
6 Downloadable Samples
NextSeq 500
Description
Bone mineral density (BMD) is a strong predictor of osteoporotic fracture. It is also one of the most heritable disease-associated quantitative traits. As a result, there has been considerable effort focused on dissecting its genetic basis. Here, we performed a genome-wide association study (GWAS) in a panel of inbred strains to identify associations influencing BMD. This analysis identified a significant (P=3.1 x 10-12) BMD locus on Chromosome 3@52.5 Mbp that replicated in two seperate inbred strain panels and overlapped a BMD quantitative trait locus (QTL) previously identified in a F2 intercross. The association mapped to a 300 Kbp region containing four genes; Gm2447, Gm20750, Cog6, and Lhfp. Â Further analysis found that Lipoma HMGIC Fusion Partner (Lhfp) was highly expressed in bone and osteoblasts and its expression was regulated by local expression QTL (eQTL) in multiple tissues. A co-expression network analysis revealed that Lhfp was strongly connected to genes involved in osteoblast differentiation. To directly evaluate its role in bone, Lhfp deficient mice (Lhfp-/-) were created using CRISPR/Cas9. Consistent with genetic and network predictions, bone marrow stromal cells (BMSCs) from Lhfp-/- displayed increased osteogenic differentiation. Lfhp-/- mice also had elevated BMD due to increased cortical bone mass. In conclusion, we used GWAS and systems genetics in mice to identify Lhfp as a regulator of osteoblast activity and bone mass. Overall design: Bones and osteoblast-derived from bone marrow stromal cells were profiles using RNA-seq from CC0016/GeniUnc mice (N=3 biological replicates per sample type)
Publication Title
Mouse genome-wide association and systems genetics identifies Lhfp as a regulator of bone mass.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 55 Downloadable Samples
Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
There is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Publication Title
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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- Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
We studied alterations in gene expression profiles of the MCF7 human breast cancer cells caused by bisphenol A, bisphenol AF and glyphosate using Illumina RNA sequencing platform. Overall design: Examination of endocrine disrupting effects of xenobiotics using the MCF7 cell line
Publication Title
Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate.
Publication Title
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 19 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate.
Publication Title
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sample Metadata Fields
Sex, Specimen part
View Samples