RNA-Seq Versus Oligonucleotide Array Assessment of Dose-Dependent TCDD-elicited Hepatic Gene Expression in Mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE62903 | GEO | 2015/02/10
SECONDARY ACCESSION(S): PRJNA266004
REPOSITORIES: GEO
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Project description:BackgroundDose-dependent differential gene expression provides critical information required for regulatory decision-making. The lower costs associated with RNA-Seq have made it the preferred technology for transcriptomic analysis. However, concordance between RNA-Seq and microarray analyses in dose response studies has not been adequately vetted.ResultsWe compared the hepatic transcriptome of C57BL/6 mice following gavage with sesame oil vehicle, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 μg/kg TCDD every 4 days for 28 days using Illumina HiSeq RNA-Sequencing (RNA-Seq) and Agilent 4 × 44 K microarrays using the same normalization and analysis approach. RNA-Seq and microarray analysis identified a total of 18,063 and 16,403 genes, respectively, that were expressed in the liver. RNA-Seq analysis for differentially expressed genes (DEGs) varied dramatically depending on the P1(t) cut-off while microarray results varied more based on the fold change criteria, although responses strongly correlated. Verification by WaferGen SmartChip QRTPCR revealed that RNA-Seq had a false discovery rate of 24% compared to 54% for microarray analysis. Dose-response modeling of RNA-Seq and microarray data demonstrated similar point of departure (POD) and ED50 estimates for common DEGs.ConclusionsThere was a strong correspondence between RNA-Seq and Agilent array transcriptome profiling when using the same samples and analysis strategy. However, RNA-Seq provided superior quantitative data, identifying more genes and DEGs, as well as qualitative information regarding identity and annotation for dose response modeling in support of regulatory decision-making.
| S-EPMC4456707 | biostudies-literature
Project description:Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure as well as compare the performance of RNA-Seq and Agilent oligonucleotide microarrays for detection and identificatioin of differentially expressed genes.
2015-02-10 | GSE62850 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-02-10 | E-GEOD-62903 | biostudies-arrayexpress
Project description:Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure as well as compare the performance of RNA-Seq and Agilent oligonucleotide microarrays for detection and identificatioin of differentially expressed genes. Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle This submission represents the Agilent microarrays component of study.
2015-02-10 | E-GEOD-62850 | biostudies-arrayexpress
Project description:Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure as well as compare the performance of RNA-Seq and Agilent oligonucleotide microarrays for detection and identificatioin of differentially expressed genes.
2015-02-10 | GSE62902 | GEO
Project description:Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure as well as compare the performance of RNA-Seq and Agilent oligonucleotide microarrays for detection and identificatioin of differentially expressed genes. Five biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
2015-02-10 | E-GEOD-62902 | biostudies-arrayexpress
Project description:We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis, and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28 d or 92 d. RNA-Seq, ChIP-Seq (2?h), and 28 d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92 d. Additional vehicle and 30 µg/kg treatment groups were allowed to recover for 36 d following the 92-d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92 days, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1?, -2, -4, -6, and -10, as well as TNF-? and IFN-?, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. In summary, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.
| S-EPMC5139066 | biostudies-literature
Project description:Dose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the liver of C57BL/6 male mice.
2017-02-28 | GSE87519 | GEO
Project description:We have previously shown that in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-elicited NAFLD progression, central carbon, glutaminolysis and serine/folate metabolism are reprogrammed to support NADPH production and ROS defenses. To further investigate underlying dose-dependent responses associated with TCDD-induced fibrosis, female C57BL/6 mice were gavaged with TCDD every 4 days (d) for 28d or 92d. RNA-Seq, ChIP-Seq (2hr), and 28d metabolomic (urine, serum, and hepatic extract) analyses were conducted with complementary serum marker assessments at 92d. Additional vehicle and 30 µg/kg treatment groups were allowed to recover for 36d following the 92d treatment regimen to examine recovery from TCDD-elicited fibrosis. Histopathology revealed dose-dependent increases in hepatic fat accumulation, inflammation, and periportal collagen deposition at 92d, with increased fibrotic severity in the recovery group. Serum proinflammatory and profibrotic interleukins-1β, -2, -4, -6, and -10, as well as TNFα and IFNγ, exhibited dose-dependent induction. An increase in glucose tolerance was observed with a concomitant 3.0-fold decrease in hepatic glycogen linked to increased ascorbic acid biosynthesis and proline metabolism, consistent with increased fibrosis. RNA-Seq identified differential expression of numerous matrisome genes including an 8.8-fold increase in Tgfb2 indicating myofibroblast activation. Further analysis suggests reprogramming of glycogen, ascorbic acid, and amino acid metabolism in support of collagen deposition and the use of proline as a substrate for ATP production via the proline cycle. Conclusion: In addition to metabolic reprogramming in support of NADPH production for ROS defense, we demonstrate that glycogen, ascorbic acid, and amino acid metabolism are also reorganized to support remodeling of the extracellular matrix, progressing to hepatic fibrosis in response to chronic injury from TCDD.
2016-09-01 | GSE81990 | GEO
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) dose-dependently induces the development of hepatic fat accumulation and inflammation with fibrosis in mice initially in the portal region. Conversely, differential gene and protein expression is first detected in the central region. To further investigate cell-specific and spatially resolved dose-dependent changes in gene expression elicited by TCDD, single-nuclei RNA sequencing and spatial transcriptomics were used for livers of male mice gavaged with TCDD every 4 days for 28 days. The proportion of 11 cell (sub)types across 131 613 nuclei dose-dependently changed with 68% of all portal and central hepatocyte nuclei in control mice being overtaken by macrophages following TCDD treatment. We identified 368 (portal fibroblasts) to 1339 (macrophages) differentially expressed genes. Spatial analyses revealed initial loss of portal identity that eventually spanned the entire liver lobule with increasing dose. Induction of R-spondin 3 (Rspo3) and pericentral Apc, suggested dysregulation of the Wnt/β-catenin signaling cascade in zonally resolved steatosis. Collectively, the integrated results suggest disruption of zonation contributes to the pattern of TCDD-elicited NAFLD pathologies.
| S-EPMC9887712 | biostudies-literature