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GSE77112
Rattus norvegicus
12 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The present study was designed to test the hypothesis that limited growth of the fetal liver in the model of maternal fasting is independent of well-characterized signaling mechanisms that are known to regulate somatic growth in adult animals.
Publication Title
Regulation of fetal liver growth in a model of diet restriction in the pregnant rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 40 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Our strategy was to manipulate mTOR signaling in vivo, then characterize the transcriptome and translating mRNA in liver tissue. In adult rats, we used the non-proliferative growth model of refeeding after a period of fasting, and the proliferative model of liver regeneration following partial hepatectomy. We also studied livers from pre-term fetal rats (embryonic day 19-20) in which fetal hepatocytes are asynchronously proliferating. All three models employed rapamycin to inhibit mTOR signaling.
Publication Title
Profiling of the fetal and adult rat liver transcriptome and translatome reveals discordant regulation by the mechanistic target of rapamycin (mTOR).
Sample Metadata Fields
Specimen part, Time
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Liver transplantation is the only therapeutic option for patients with end-stage liver disease. The shortage of donor organs has led to the search for alternative therapies to restore liver function and bridge patients to transplantation. Our previous work has shown that the proliferation of late gestation E19 fetal hepatocytes is mitogen-independent. This is manifested as differences in the control of ribosome biogenesis, global translation, cell cycle progression and gene expression. In the present study, we investigated whether E19 fetal hepatocytes would engraft and repopulate an injured adult liver.
Publication Title
Engraftment and Repopulation Potential of Late Gestation Fetal Rat Hepatocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
DNA methylation is an important epigenetic control mechanism that has been shown to be associated with gene silencing through the course of development, maturation and aging. However, only limited data are available regarding the relationship between methylation and gene expression in human development. We analyzed the methylomes and transcriptomes of three human fetal liver samples (gestational age 20-22 weeks) and three adult human liver samples. Genes whose expression differed between fetal and adult numbered 7,673. Adult overexpression was associated with metabolic pathways and, in particular, cytochrome P450 enzymes, while fetal overexpression reflected enrichment for DNA replication and repair. Analysis for DNA methylation using the Illumina Infinium 450K HumanMethylation BeadChip showed that 42% of the quality filtered 426,154 methylation sites differed significantly between adult and fetal tissue (q0.05). Differences were small; 69% of the significant sites differed in their mean methylation beta value by 0.2. There was a trend among all sites toward higher methylation in the adult samples with the most frequent difference in beta being 0.1. Characterization of the relationship between methylation and expression revealed a clear difference between fetus and adult. Methylation of genes overexpressed in fetal liver showed the same pattern as seen for genes that were similarly expressed in fetal and adult liver. In contrast, adult overexpressed genes showed fetal hypermethylation that differed from the similarly expressed genes. An examination of gene region-specific methylation showed that sites proximal to the transcription start site or within the first exon with a significant fetal-adult difference in beta (>0.2) showed an inverse relationship with gene expression. Nearly half of the CpGs in human liver show a significant difference in methylation comparing fetal and adult samples. Sites proximal to the transcription start site or within the first exon that show a transition from hypermethylation in the fetus to hypomethylation or intermediate methylation in the adult are associated with inverse changes in gene expression. In contrast, increases in methylation going from fetal to adult are not associated with fetal-to-adult decreased expression. These findings indicate fundamentally different roles for and/or regulation of DNA methylation in human fetal and adult liver.
Publication Title
Patterns of gene expression and DNA methylation in human fetal and adult liver.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells.
Publication Title
A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Little is known about the role of the transcription factor PPAR/d in liver. Here we set out to better elucidate the function of PPAR/d in liver by comparing the effect of PPARa and PPAR/d deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARa and PPAR/d deletion was similar, whereas in fasted state the effect of PPARa deletion was much more pronounced, consistent with the pattern of gene expression of PPARa and PPAR/d. Minor overlap was found between PPARa- and PPAR/d-dependent gene regulation in liver. Pathways upregulated by PPAR/d deletion were connected to innate immunity. Pathways downregulated by PPAR/d deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPAR/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPAR/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma -hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPAR/d-/- mice. Our data indicate a role for PPAR/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting.
Publication Title
Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 92 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dietary fatty acids have myriads of effects on human health and disease. Many of these effects are likely achieved by altering expression of genes. Several transcription factors have been shown to be responsive to fatty acids, including SREBP-1c, NF-kB, RXRs, LXRs, FXR, HNF4, and PPARs. However, the relative importance of these transcription factors in regulation of gene expression by dietary fatty acids remains unclear. Here, we take advantage of a unique experimental design using synthetic triglycerides composed of one single fatty acid in combination with gene expression profiling to examine the acute effects of individual dietary fatty acids on hepatic gene expression in mice. The dietary interventions were performed in parallel in wild-type and PPAR-/- mice, enabling the determination of the specific contribution of PPAR. Depending on chain length and degree of saturation, dietary fatty acids caused a statistically significant change in expression of over 400 genes. Surprisingly, the far majority of genes regulated by dietary fatty acids in wild-type mice were unaltered in mice lacking PPAR, indicating PPAR-dependent regulation. We conclude that the effects of dietary fatty acids on hepatic gene expression are almost entirely mediated by PPAR, indicating that PPAR dominates fatty acid-dependent gene regulation in liver.
Publication Title
Effect of synthetic dietary triglycerides: a novel research paradigm for nutrigenomics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was to identify differentially expressed genes in laser-capture microdissected (LCM) invasive mammary carcinomas (IMCs).
Publication Title
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) but not PPARalpha serves as a plasma free fatty acid sensor in liver.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant dose-dense docetaxel treatment using gene expression profiling on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with 75 mg/m2 IV of docetaxel on day 1 of each cycle every 2 weeks x 4 cycles . Tumor tissue from pretreatment biopsies was obtained from 12 patients enrolled in the study. Gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR).
Publication Title
Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.
Sample Metadata Fields
Specimen part, Treatment
View Samples