Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA210891 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In this study, we evaluated the utility of microRNA (miRNA) profiling in female B6C3F1 mouse liver to indicate mechanisms of liver perturbation due to short-term exposure of the known rodent liver hepatotoxicant and carcinogen, furan. Analyses indicated a robust dose response for 34 miRNAs to furan and involvement of p53-linked pathways in furan-mediated hepatotoxicity. Overall, these results indicate mechanistic involvement of miRNA in furan carcinogenicity and provide evidence of their potential utility as accessible biomarkers of exposure and disease.
2023-09-05 | GSE224206 | GEO
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. Adult female B6C3F1 mice were exposed to 1, 2, 4 or 8 mg/kg bw furan or vehicle control (corn oil) for three weeks and sacrificed four hours after the final exposure. In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice exposed to furan for 3 weeks at four different doses: 1, 2, 4 or 8 mg/kg bw furan (or vehicle control) and sacrificed four hours after the final exposure. Each dose group had 4-5 biological replicates. There were a total of 25 samples included in the final analysis. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent).
2014-01-10 | E-GEOD-48644 | biostudies-arrayexpress
Project description:PR-SET7-mediated histone-4 lysine-20 methylation has been implicated in mitotic condensation, DNA damage response and replication licencing. Here we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis with unusual features of autophagy, termed "endonucleosis". Necrotic death was accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic-regenerative cycles coupled with oncogenic STAT3 activation replaced pre-existing hepatocytes with hepatocellular carcinoma derived entirely from ductal progenitor cells. Hepatocellular carcinoma in these mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes. Mice carrying hepatocyte specific inactivation of PR-SET7 were generated in order to investigate the function of PR-SET7 histone methyl transferase in liver organogenesis, hepatocyte proliferation and liver regeneration. P15 WT mice were injected intra-peritoneally (ip) with 25ml per kg DEN (diethyl nitrosamine). Mice were examined for RNA expression at 8 months old.
2014-08-01 | E-GEOD-49555 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. Adult female B6C3F1 mice were exposed to 1, 2, 4 or 8 mg/kg bw furan or vehicle control (corn oil) for three weeks and sacrificed four hours after the final exposure.
2014-01-10 | GSE48644 | GEO
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action. In this study we examined the transcriptional response in liver tissue of female B6C3F1 mice to BrdU treatment (in drinking water for 5 days before sacrifice). This was a toxicogenomic study in which mice were also exposed to 0, 1 or 8 mg/kg bw furan (by oral gavage) for 3 weeks. Mice were sacrificed four hours after the final furan exposure. Each dose group had 4-5 biological replicates. We used a two-colour reference design and SurePrint G3 Mouse GE 8x60K microarrays (Agilent). Please note that data for all non-BrdU treated animals was previously reported in GEO [GSE48644]. All samples (with or without BrdU) were part of the same randomized block design for the microarrays.
2014-07-01 | E-GEOD-54078 | biostudies-arrayexpress
Project description:Furan is a mouse and rat hepatocarcinogen. We sought to determine the dose-dependent changes in gene expression upon exposure of B6C3F1 mice to furan in order to better understand furan’s mode of action.
2014-07-01 | GSE54078 | GEO
Project description:Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, non-alcoholic fatty liver disease (NAFLD) is gaining importance. As the disease progresses it can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in NAFLD development, but the molecular mechanisms responsible for disease development remained unresolved. Here, we uncover a strong downregulation of the PI3K-AKT pathway and an upregulation of the MAPK pathway in primary hepatocytes from a preclinical model fed with a Western diet (WD). Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveals a patient-specific variability in basal MET phosphorylation, which correlates with the outcome of patients after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.
2024-01-16 | MODEL2306280002 | BioModels
Project description:The equilibrium between cellular differentiation and proliferation is fundamental for tissue homeostasis. This is particularly important for the liver, a highly differentiated organ with systemic metabolic functions still endowed with unparalleled regenerative potential. Hepatocellular de-differentiation and uncontrolled proliferation are at the basis of liver carcinogenesis. We have identified SLU7, a pre-mRNA splicing regulator inhibited in hepatocarcinoma as a pivotal gene for hepatocellular homeostasis. SLU7 knockdown in human liver cells and mouse liver resulted in profound changes in pre-mRNA splicing and gene expression, leading to impaired glucose and lipid metabolism, refractoriness to key metabolic hormones, and reversion to a fetal-like gene expression pattern. Hepatocellular proliferation and a switch to a tumor-like glycolytic phenotype were also observed. Mechanistically, SLU7 governed the splicing and/or expression of essential genes for hepatocellular differentiation like SRSF3 and HNF4a, and was identified as a critical factor in cAMP-regulated gene transcription. SLU7 is therefore central for hepatocyte identity and quiescence. The expression of the splicing factor SLU7 in the human hepatocellular carcinoma cell line PLC/PRF/5 was knocked down with specific siRNAs (siSlu7). An irrelevant siRNA (siGL2) was used as negative control. The RNAto perfrom the array analysis was extracted 48h after transfection.
2014-05-29 | E-GEOD-54090 | biostudies-arrayexpress
Project description:The cell of origin of hepatoblastoma in humans and mice (HB) is unknown; it has been hypothesized to be a transformed hepatocyte, an oval cell, or a multipotent hepatic progenitor cell. In mice, the current dogma is that HBs arise within hepatocellular neoplasms as a result of further transformation from a neoplastic hepatocyte. However, there is little evidence in the literature to support a direct relationship between these two cell types. Furthermore, due to differences in etiology and development of hepatoblastoma between mice and humans, many have questioned the relevance of these tumors in hazard identification and risk assessment. In order to better understand the relationship between hepatocellular carcinoma and hepatoblastoma, as well as better determine the molecular similarities between mouse and human hepatoblastoma, global gene expression analysis and targeted Hras and Ctnnb1 mutation analysis were performed using concurrent hepatoblastoma, hepatocellular carcinoma, and associated normal adjacent liver (in the context of vehicle control liver) samples from a recent National Toxicology Program chronic bioassay. The data from this study provides a better understanding of the origins of hepatoblastoma in the B6C3F1 mice and the relevance of mouse hepatoblastoma to humans when considering chemical exposures of potential human cancer risk. Compare mouse hepatoblastoma versus adjacent hepatocellular carcinomas versus adjacent non-tumor liver and vehicle control normal liver, 6 replicates each group.
2015-09-01 | E-GEOD-67316 | biostudies-arrayexpress
Project description:PR-SET7-mediated histone-4 lysine-20 methylation has been implicated in mitotic condensation, DNA damage response and replication licencing. Here we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis with unusual features of autophagy, termed "endonucleosis". Necrotic death was accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic-regenerative cycles coupled with oncogenic STAT3 activation replaced pre-existing hepatocytes with hepatocellular carcinoma derived entirely from ductal progenitor cells. Hepatocellular carcinoma in these mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes.
2014-08-01 | GSE49555 | GEO