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RNA-seq gene expression profiling of protein coding and lncRNA genes in cytoplasmic RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G174]

ABSTRACT: PolyA-selected RNA was isolated from the cytoplasmic fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE160712 | GEO | 2021/03/01

REPOSITORIES: GEO

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RNA-seq gene expression profiling of protein coding and lncRNA genes in nucleoplasmic RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G176]

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RNA-seq gene expression profiling of protein coding and lncRNA genes in nuclear RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G175]

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Project description:PolyA-selected RNA was isolated from the chromatin bound fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with 3 mg/kg TCPOBOP disolved in corn oil, or corn oil vehicle, for 27 hr. These samples are part of a study where we characterize global patterns of expression, maturation and localization for both lncRNA and protein coding gene transcripts in mouse liver, and where we identify candidate regulatory lncRNAs that may be important for a variety of hepatic functions, based on their co-localized within topologically associating domains, or their transcription divergent, antisense or intergenic to protein coding genes associated with key pathways linked to hepatic physiology and disease.

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RNA-seq gene expression profiling of protein coding and lncRNA genes in chromatin bound (non-polyA selected) RNA from livers of male and female mice, with or without exposure to TCPOBOP, a CAR (Nr1i3) agonist ligand [G177]

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RNA-seq gene expression profiling of RefSeq genes in nuclear RNA from livers of mice treated with the nuclear receptor CAR (Nr1i3) agonist ligand TCPOBOP for 2 week or for 8 week.

Project description:PolyA-selected RNA was isolated from the nuclear fraction of frozen liver tissue from adult male and female ICR/CD1 mice that were treated with a TCPOBOP delivered using either a Low Corn Oil vehice or a High Corn Oil vehicle regimen. Livers were collected and nuclear RNA purified and analyzed either 2 week or 8 weeks after initiating TCPOBOP treatment. These samples are part of a study designed to elucidate genes and gene-based mechanisms underlying TCPOBOP-disrupted liver metabolic dysfunction, including the pericentral steatosis seen within 2 weeks of the initial TCPOBOP exposure. Major findings of this work included the following: Early (1-day) TCPOBOP transcriptional responses were enriched for CAR-bound primary response genes, and for lipogenesis and xenobiotic metabolism and oxidative stress protection pathways; late (2-wk) TCPOBOP responses included many CAR binding-independent secondary response genes, with enrichment for macrophage activation, immune response and cytokine and reactive oxygen species production. Late upstream regulators specific to TCPOBOP-exposed male liver were linked to pro-inflammatory responses and hepatocellular carcinoma progression. TCPOBOP administered weekly to male mice using a high corn oil vehicle activated carbohydrate-responsive transcription factor (MLXIPL)-regulated target genes, dysregulated mitochondrial respiratory and translation regulatory pathways, and induced more advanced liver pathology. Overall, TCPOBOP exposure recapitulated histological and gene expression changes characteristic of emerging steatotic liver disease, including secondary gene responses in liver non-parenchymal cells indicative of transition to a more advanced disease state.

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Project description:The nuclear receptor CAR (constitutive androstane receptor) mediates the effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) on gene transcription. To investigate the relative role of CAR and also PXR in the induction response, cDNA arrays were generated containing 120 (Sterolgene V1) genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with TCPOBOP for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of CAR receptor in the expression of genes involved in drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 10mg/kg TCPOBOP or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the TCPOBOP treated ones and hybridized to Sterolgene V1 arrays.

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Murine livers: Control vs. Liver Fibrosis

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