Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA203211 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptomic profiling; Determination of the transcriptomic similarity between Egfr fl/fl and Met fl/fl progenitor cells isolated from excised livers (n=3, each) Profiling of hepatic progenitor cells
2013-09-05 | E-GEOD-46981 | biostudies-arrayexpress
Project description:Transcriptomic profiling; Determination of the transcriptomic similarity between Egfr fl/fl and Met fl/fl progenitor cells isolated from excised livers (n=3, each)
2013-09-05 | GSE46981 | GEO
Project description:MET and EGFR receptor tyrosine kinases are crucial for liver regeneration and normal hepatocyte function. Recently we demonstrated that in mice, combined inhibition of these two signaling pathways abolished liver regeneration following hepatectomy, with subsequent hepatic failure and death at 15-18 days post-resection. Morbidity was associated with distinct and specific alterations in important downstream signaling pathways that led to a decrease in hepatocyte volume, reduced proliferation, and shutdown of many essential hepatocyte functions such as fatty acid synthesis, urea cycle, and mitochondrial functions. In the present study we explore the role of MET and EGFR signaling in resting mouse livers that are not subjected to hepatectomy. Mice with combined disruption of MET and EGFR signaling (Delta MET + EGFRi) were noticeably sick by 10 day and died at 12-14 days. Delta MET + EGFRi mice showed decreased liver to body weight ratios, increased apoptosis in non-parenchymal cells, impaired liver metabolic functions, and activation of distinct, downstream signaling pathways related to inflammation, cell death, and survival. Conclusion: The present study demonstrates that in addition to controlling the regenerative response, MET and EGFR synergistically control baseline liver homeostasis in normal mice in such a way that their combined disruption leads to liver failure and death. We used microarrays to detail the global programme of gene expression in Delta MET + EGFRi mice liver vs control mice liver
2018-07-09 | GSE116307 | GEO
Project description:HGF has been reported to have both positive and negative effects on carcinogenesis. Here we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/-; MetLivKO) treated with N-nitrosodiethylamine (DEN) developed significantly more and bigger tumors and with a shorter latency as compared with control (wt/wt, AlbCre+/-; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with DEN also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and upregulation of superoxide dismutase 1 (Sod1) and heat shock protein 70 (Hsp70), all consistent with increased oxidative stress. Likewise, gene expression profiling performed at 3 and 5 months after DEN treatment revealed upregulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met-deficiency were reversed by chronic oral administration of anti-oxidant N-acetylcysteine (NAC). NAC blocked the EGFR activation and reduced the DEN-initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of DEN-induced hepatocarcinogenesis. Keywords: compound treatment design
2008-08-09 | GSE8747 | GEO
Project description:HGF has been reported to have both positive and negative effects on carcinogenesis. Here we show that the loss of c-Met signaling in hepatocytes enhanced rather than suppressed the early stages of chemical hepatocarcinogenesis. c-Met conditional knockout mice (c-metfl/fl, AlbCre+/-; MetLivKO) treated with N-nitrosodiethylamine (DEN) developed significantly more and bigger tumors and with a shorter latency as compared with control (wt/wt, AlbCre+/-; Cre-Ctrl) mice. Accelerated tumor development was associated with increased rate of cell proliferation and prolonged activation of epidermal growth factor receptor (EGFR) signaling. MetLivKO livers treated with DEN also displayed elevated lipid peroxidation, decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), and upregulation of superoxide dismutase 1 (Sod1) and heat shock protein 70 (Hsp70), all consistent with increased oxidative stress. Likewise, gene expression profiling performed at 3 and 5 months after DEN treatment revealed upregulation of genes associated with cell proliferation and stress responses in c-Met mutant livers. The negative effects of c-Met-deficiency were reversed by chronic oral administration of anti-oxidant N-acetylcysteine (NAC). NAC blocked the EGFR activation and reduced the DEN-initiated hepatocarcinogenesis to the levels of Cre-Ctrl mice. These results argue that intact HGF/c-Met signaling is essential for maintaining normal redox homeostasis in the liver and has tumor suppressor effect(s) during the early stages of DEN-induced hepatocarcinogenesis. Keywords: compound treatment design To address a role for c-Met in liver carcinogenesis, we employed a hepatocyte specific c-Met conditional knockout mouse model generated in our laboratory. Mice received a single intraperitoneal injection of 10 µg/g body weight of N-nitrosodiethylamine (DEN) (Sigma-Aldrich, Inc., St. Louis, MO, USA) at 14 days of age. Livers were examined at 3 and 5 months after DEN injection. Expression profiling was conducted on five animals from each genotype per time point. Total RNA pooled from five wild-type B6/129 strain mouse livers was used as universal hybridization reference. All experiments were performed in duplicates following a dye-swapping design. Arrays were scanned with a GenePix 4000A scanner (Axon Instruments Ltd., Burlingame, CA) in a way to achieve optimal signal intensity at both channels with less than 1% saturated spots. After excluding the invalid features, all arrays were normalized to the 50th percentile of the median signal intensity using the mAdb data analysis suite (http://nciarray.nci.nih.gov/). Unsupervised cluster analysis was performed with the Cluster and TreeView programs (http://rana.lbl.gov/EisenSoftware.htm). The BRB ArrayTools V3.3.0 software package (Biometric Research Branch, National Cancer Institute; http://linus.nci.nih.gov/BRB-ArrayTools.html) was used for the supervised comparison. Differentially expressed genes were selected using a univariate 2-sample t-test (P<0.001) with a random variance model (15). Functional classification of the significant genes was based on the Gene Ontology (GO) annotations (www.geneontology.org).
2008-08-09 | E-GEOD-8747 | biostudies-arrayexpress
Project description:Purpose: The goal of this study was to determine biological consequences during liver regeneration following partial hepatectomy in mice by next-generation sequencing. A particular interest was to compare mice with either a floxed b-PDGFR allele to mice that harbored a deletion of b-PDGFR in hepatic stellate cells (HSCs), by crossing b-PDGFR fl/fl mice with transgenic GFAP-Cre mice. Methods: b-PDGFR fl/fl mice or mice with a HSC-specific deletion of b-PDGFR underwent either sham operation or 70% partial hepatectomy. Following 72 hours, livers were collected and total RNA was extracted using tizol, followed by a purification using Quiagen spin columns including an on-column DNAse digestion step. Conclusion: Our study represents a detailed analysis of hepatic transcriptome, with biologic replicates, generated by RNA-seq technology of livers following sham operation or partial hepatectomy in b-PDGFR fl/fl mice or b-PDGFRfl/fl/GRAP-Cre mice. Whole liver mRNA profiles of sham operated livers or livers collected 72hours after partial hepatectomy of beta-PDGFR fl/fl and beta-PDGFR fl/fl/GFAP-Cre (creating a hepatic stellate cell-specific deletion of b-PDGFR) mice were generated by deep sequencing, in duplicate, using Illumina HiSeq2000.
2013-11-08 | E-GEOD-52234 | biostudies-arrayexpress
Project description:Analysis of single cell RNA-seq, CITE-seq data and bulk RNA-seq data on cells isolated from the livers of mice following PBS and APAP (paracetamol/acetaminophen) administration. Spatial Transcriptomics analysis was performed using 10x Visium platform on mouse livers 48hrs post PBS or APAP administration. We also analysed single cell RNA-seq data on CD64+F4/80+ macrophages isolated from the livers of Trem2 fl/fl mice and CD64CRE Trem2 fl/fl mice.
2024-10-30 | GSE280652 | GEO
Project description:Analysis of single cell RNA-seq, CITE-seq data and bulk RNA-seq data on cells isolated from the livers of mice following PBS and APAP (paracetamol/acetaminophen) administration. Spatial Transcriptomics analysis was performed using 10x Visium platform on mouse livers 48hrs post PBS or APAP administration. We also analysed single cell RNA-seq data on CD64+F4/80+ macrophages isolated from the livers of Trem2 fl/fl mice and CD64CRE Trem2 fl/fl mice.
2024-10-30 | GSE280514 | GEO
Project description:Analysis of single cell RNA-seq, CITE-seq data and bulk RNA-seq data on cells isolated from the livers of mice following PBS and APAP (paracetamol/acetaminophen) administration. Spatial Transcriptomics analysis was performed using 10x Visium platform on mouse livers 48hrs post PBS or APAP administration. We also analysed single cell RNA-seq data on CD64+F4/80+ macrophages isolated from the livers of Trem2 fl/fl mice and CD64CRE Trem2 fl/fl mice.
2024-10-30 | GSE280515 | GEO
Project description:To identify HGF/Met regulated genes, we performed expression microarray analysis after inducible activation of Met receptor in primary cultures of hepatocytes established from wild-type control (Alb-Cre +/-) and Met conditional knockout mice (Alb-Cre +/-; Met Fl/Fl). Keywords: time series design
2006-10-02 | GSE4451 | GEO