Similar Datasets
Project description:Fmo5(-/-) mouse: liver transcriptomics
| PRJNA748725 | ENA
Project description:We report liver transcript profiling by RNA sequencing of Atp7b-/- and wild type mice at six weeks of age. Transcriptional network analysis of RNA-seq data reveals a highly interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors.
2017-12-01 | GSE95260 | GEO
Project description:Abstract The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell sub-populations. In this study, we performed snRNA-seq of a liver sample to identify sub-populations of cells based on nuclear transcriptomics. In 4,282 single nuclei we detected on average 1,377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p<0.05) for 7,682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry (MS) proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r=0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidines toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.
2020-12-21 | PXD017610 | Pride
Project 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. Ten female rats were fed drinking water containing 0.1ppb Roundup formulation (50 ng/L glyphosate equivalent dilution). Ten control female rats were fed untreated drinking water. Samples of liver and kidney were taken for gene expression analysis.
2015-09-04 | E-GEOD-66058 | biostudies-arrayexpress
Project description:Using high throughput sequencing we report H3K9 methylation status in mouse liver upon refeeding a high carb diet. We find accumulation of H3K9me2 in genes that are typically repressed upon refeeding, confirming that H3K9me2 methylation works to repress transcription.
2022-05-01 | GSE130855 | GEO
Project description:Aging is an inevitable process in life that leads to numerous systemic effects on the human body. Here, we investigated systematically the effect of aging on the liver using a rat model of aging using data-driven approaches. We performed systems biology approaches to analyze genome-wide transcriptomics data from liver samples obtained from 3- and 19 months old rats. We observed significant alterations in multiple biological processes, including (1) disruption of mitochondrial functions and protein synthesis, and (2) activation of immune and inflammation pathways and lipid metabolism. We validated our results in two independent aging datasets. Finally, we demonstrated the power of the co-expression network to identify novel driver genes for liver aging and confirmed our findings in human aging subjects. Overall, we identified and validated a liver-specific gene, PCSK9, as a potential therapeutic target for attenuating the aging effect on the liver.
2023-09-08 | GSE210371 | GEO
Project description:We report the effect of NAFLD on liver gene expression changes that could impact tetrachloroethhylene metabolism Methods: We fed male C57Bl/6J mice a base diet (BD), high fat (HFD), or methionine/choline/folate deficient high fat diet (MCD) for 8 weeks and then treated them with vehicle or tetrachloroethylene (PERC, 300 mg/kg ig). We only report "basal" differences herein (aka vehicle-treated). Results: We report that there were diet-specific differences in xenobiotic metabolizing genes, and that these genes may be responsible for NAFLD-induced disruption in PERC metabolism
2017-01-05 | GSE93132 | GEO
Project description:The goal of this study is to obtain an expression profile of regenerating mouse livers. We used microarray analysis to study the gene groups coordinately expressed temporally during mouse a liver regeneration. One of the syn-expression groups that showed a sharp rise in gene expression immediately after hepatectomy contains a set pancreatic exocrine genes. The syn-expression profile of pancreatic genes and the pancreatic-specific transcription factors Ptf1a and Ipf1 was confirmed using real-time PCR. Electron microscopic examination showed the presence of morphological features reminiscent of pancreatic acinar cells with the presence of characteristic zymogen granules and ER organization. These results indicate that there is a transient liver-to-pancreas transdifferentiation event at the beginning of liver regeneration. A strong coordinated up-regulation of pancreatic genes was found to accompany the injury response in the pancreas, suggesting a compensatory mechanism for pancreatic functions. There seems to be a relationship between the induction of pancreatic genes and acute phase response at the beginning of liver regeneration. Keywords: gene expression array-based (RNA / in situ oligonucleotide)
2007-12-13 | GSE4528 | GEO
Project description:Although epigenetic mechanisms, such as specific histone modifications, control common and cell-specific genetic programs, a role for histone modifying enzymes in liver metabolism and disease has not been investigated. This report demonstrates that the combined loss of the histone methyltransferases EZH1 and EZH2 in mouse hepatocytes led to the disruption of H3K27me3 homeostasis by age three months, simple fatty liver by age six months and fatal fibrosis by age 15 months. Global and gene-specific reduction of H3K27me3 marks paralleled a concomitant increase of H3K4me3 marks at genes associated with chronic liver disease. Advanced disease was accompanied by widespread infiltration of immune cells, an increase of activated hepatic stellate cells and collagen deposition. Expression of genes from the cytochrome P450 family that control drug metabolism was already deregulated by age two months and mice were fatally hypersensitive to carbon tetrachloride (CCl4). These genetic experiments, for the first time, illustrate that the simple loss of EZH1/EZH2, which results in the disruption of epigenetic modifications, is sufficient for the progression of fatal liver disease. RNA-seq and ChIP-seq were performed in liver tissues.
2013-12-24 | E-GEOD-53627 | biostudies-arrayexpress
Project description:Exam change in the whole-cell and nuclear proteome circadian proteome in response to environmental circadian disruption (ECD) in mouse liver
2024-06-12 | PXD052085 | Pride