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GSE60693
Mus musculus
345 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Rat Expression 230A Array (rae230a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 167 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcino- genesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARKO -PXRKO ), double humanized CAR and PXR (CARh - PXRh), and wild-type C57BL/6 mice. Wild-type and CARh-PXRh mouse livers exhibited temporally and quantitatively similar tran- scriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were ob- served with peak expression occurring between 1 and 7 days PB ex- posure. All these transcriptional responses were absent in CARKO- PXRKO mouse livers and largely reversible in wild-type and CARh - PXRh mouse livers following 91 days of PB exposure and a subse- quent 4-week recovery period. Furthermore, PB-mediated upregu- lation of the noncoding RNA Meg3, which has recently been associ- ated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARh-PXRh mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.
Publication Title
Phenobarbital induces cell cycle transcriptional responses in mouse liver humanized for constitutive androstane and pregnane x receptors.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject, Time
View Samples- Mus musculus
- 69 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for -catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and -catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds.
Publication Title
Identification of Dlk1-Dio3 imprinted gene cluster noncoding RNAs as novel candidate biomarkers for liver tumor promotion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 212 Downloadable Samples
IlluminaHiSeq2500
Description
Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. Yet the in vivo expression dynamics and molecular pathways regulated by these molecules are less well understood. Here, we leveraged a cohort of 13 lncRNA null-mutant mouse models to investigate the spatio-temporal expression of lncRNAs in the developing and adult brain. We observed a wide range of different spatio-temporal expression profiles in the brain. Several lncRNAs are differentially expressed both in time and space, and others present highly restricted expression in only selected brain regions. We further explore the consequent transcriptome alterations after loss of these lncRNA loci, and demonstrate altered regulation of a large variety of cellular pathways and processes. We further found that 6/13 lncRNA null-mutant strains significantly affect the expression of several neighboring protein-coding genes, in a cis-like manner. This resource provides insight into the expression patterns and potential effect of lncRNA loci in the developing and adult mammalian brain, and allows future examination of the specific functional relevance of these genes in neural development, brain function, and disease. We have sequenced wildtype and mutant whole brains from a cohort of 13 lncRNA knockout mouse strains at two developmetal timepoints (E14.5 and adult). Overall design: Comparison between wildtype and mutant whole brains transcriptomes in 13 lncRNA mutant strains at two different timepoints. Please note that for each knockout strain there are KO_E14.5 and KO_Adult samples, however for WT, each KO strain was compared to a cohort of 14 WTs (N3 background) and 3 WTs (N2.5 background) at either Adult or E14.5 timepoint. So in total there are 14 WT_Adult and 14 WT_E14.5 and in each differential analysis the 2 or 3 KOs (in N3 background) were compared to this entire cohort at the respective timepoint; a cohort of 3 WT_adult (N2.5) or 3 WT_E14.5 samples compared to other N2.5 KO samples at the respective timepoint. Thus, each processed data file was generated by comparing each KO strain to a cohort of WTs (at either Adult or E14.5 timepoint; ko_vs_WT_Adult or ko_vs_WT_embryonic). The mouse strain (background) used in these experiments a cross between 129 and C57BL/6 in the third generation (N3) of breeding in the C57BL/6 line, with the exception of the KANTR mice, which are N2.5.
Publication Title
Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain.
Sample Metadata Fields
No sample metadata fields
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