Analysis of gene expression changes induced in wild-type or Atf6a-/- mice by treatment with tunicamycin
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: David Rutkowski
PROVIDER: E-GEOD-48939 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a “bottom-up” approach to infer pathways in the genetic regulation of lipid metabolism by the UPR. We used a functional genomics to link gene expression patterns taken from microarray data to the severity and persistence of ER stress, using mice lacking the UPR signaling molecule ATF6α. This approach revealed that functionally related genes clustered into a small number of distinct expression profiles, and that lipid oxidation and efflux were targets for coordinated transcriptional suppression during ER stress.Our results establish a framework for hepatic gene regulation during ER stress. Atf6a-/- or +/+ mice of variable age and gender were injected intraperitoneally with 1 mg/kg tunicamycin or vehicle. 3 separate mice were used in each group. 34h after injection, mice were sacrificed and total RNA was prepared from resected livers.
2013-09-04 | E-GEOD-48935 | biostudies-arrayexpress
Project description:Protein misfolding stress in the endoplasmic reticulum (ER) leads to dysregulation of lipid metabolism in the liver, and ER stress is associated with human diseases that are accompanied by hepatic lipid accumulation, including obesity, alcoholism, and viral hepatitis; yet the pathways leading from ER stress to the regulation of lipid metabolism are poorly understood. Working exclusively in vivo, we used a “bottom-up” approach to infer pathways in the genetic regulation of lipid metabolism by the UPR. We used a functional genomics to link gene expression patterns taken from microarray data to the severity and persistence of ER stress, using mice lacking the UPR signaling molecule ATF6α. This approach revealed that functionally related genes clustered into a small number of distinct expression profiles, and that lipid oxidation and efflux were targets for coordinated transcriptional suppression during ER stress.Our results establish a framework for hepatic gene regulation during ER stress. Atf6a-/- or +/+ mice of variable age and gender were injected intraperitoneally with 2 mg/kg tunicamycin or vehicle. 3 separate mice were used in each group. 8h after injection, mice were sacrificed and total RNA was prepared from resected livers.
2013-09-04 | E-GEOD-48932 | biostudies-arrayexpress
Project description:Differences in gene expression in the liver of three strains of female mice with identical AhRb2 genotype treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin
2008-03-21 | E-MEXP-1231 | biostudies-arrayexpress
Project description:Understanding congenital liver disease requires elucidation of the signaling pathways and transcriptional events in the developing liver. Comprehensive assessment of gene expression between 10.5 and 16.5 dpc in the developing mouse liver and comparison with adult liver and non-hepatic embryonic tissue was validated with real-time PCR and in situ hybridization. The broad nature of the analysis provides insights into patterns of genetic control of hepatogenesis. Pathways implicated in human disease are highly regulated at the transcriptional level. Rather than activating or inhibiting a pathway or biological process by altering the expression of a single signaling molecule, transcriptional changes in large numbers of genes in a pathway or process are regulated in a coordinated manner. For example, both TGF-beta and Notch signaling is inhibited during hepatogenesis not just by decreasing transcription of multiple pathway members, but also with a complementary increase in the transcription of a pathway inhibitor. Similarly, genes related to specific biological processes exhibit strong temporal synchronization in which multiple members of the pathway have similar transcriptional regulation over time. Global coordination of signaling or functional families at the transcriptional level may be a mechanism to produce robustness of the desired outcomes. In addition, this comprehensive analysis provides a database for the further study of transcriptional events during liver development by identifying liver-specific, highly regulated genes. Experiment Overall Design: In order to provide transcriptional profile of the developing liver compared both to normal adult liver and non-hepatic embryonic tissueswe performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for embryonic liver samples at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc), embryo-minus liver tissues at 10.5, 11.5, 12.5, and 14.5 dpc, and normal 10-week-old adult mouse liver. Each sample consisted of at least five embryos.
2008-06-11 | E-GEOD-11201 | biostudies-arrayexpress
Project description:Normal adult liver is uniquely capable of renewal; and repair after injury. Whether this response; represents simple hyperplasia of various liver elements; or requires recapitulation of the genetic program of; the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferationassociated genes. Consistent with these findings, realtime polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level, restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury. Experiment Overall Design: In order to elucidate the molecular similarities between regenerating and developing liver, we performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for targets at 0, 1, 2, 6, 12, 18, 24, 30, 48, and 72 hours after partial hepatectomy and at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc). Experiment Overall Design: Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.
2007-11-15 | E-GEOD-6998 | biostudies-arrayexpress
Project description:The choroid plexus (CP) constitutes one of the blood–brain barriers – the blood cerebrospinal fluid barrier. It is formed by a monolayer of epithelial cells located within the brain ventricles and in addition to be responsible for the formation of the cerebrospinal fluid (CSF) is ideally positioned to transmit signals into and out of the brain. Specifically, here, we evaluated the overall kinetic response of the mouse CP to peripheral administration of lipopolysaccharide (LPS) that is the Gram-negative bacteria cell wall. This study shows that as soon as 1h after the injection, the CP responds by altering the expression of several genes. This response reaches a maximum at 3h and returns to the basal profile for most of the transcripts at 72h. To do this analysis we compared the CP transcriptome of LPS injected animals with the CP transcriptome of saline injected animals and using this we also dissect the CP basal transcriptome. From this analysis we confirm that the genes most highly expressed were those implicated in energy metabolism (oxidative phosphorylation, glycolysis/gluconeogenesis) and in ribosomal function, which is in agreement with the secretory nature of the CP. Finally, we also describe genes not previously identified as being expressed in the basal CP. Gene expression study in choroid plexus. Time series after acute LPS treatment
2010-08-19 | E-GEOD-23714 | biostudies-arrayexpress
Project description:A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net). Trascriptional profiling of mouse fetal liver during development.
2008-12-19 | E-MEXP-1853 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series:; GSE13221: (AKR/J x PyMT)F1 versus (DBA/2J x PyMT)F1 tumor expression data; GSE13222: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 blood expression data; GSE13223: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 bone marrow expression data; GSE13224: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 lung expression data; GSE13225: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 spleen expression data; GSE13227: (AKR/J x FVB/NJ)F1 versus (DBA/2J x FVB)F1 Thymus expression data; GSE13230: Met1 or DB7 tumor gene expression Experiment Overall Design: Refer to individual Series
2008-12-05 | E-GEOD-13231 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1, and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia. Hepatic mRNA profiles of C57BL/6J female mice treated with LNA against miR-29a, miR-29b and miR-29c versus saline.
2015-08-07 | E-GEOD-63493 | biostudies-arrayexpress
Project description:Background; In the postabsorptive state, the portal-drained viscera are a major energy consumer, but a comprehensive overview of the adaptive fasting response in the liver is lacking. Hence, gene-expression profiling, pathway, network and gene-set enrichment analysis and immunohistochemistry were carried out on mouse liver after 0, 12, 24, and 72 hours of fasting. Results; Liver weight has fallen to 50% of control after three days of fasting, hepatocyte size was reduced with no apparent increase in apoptosis, while the basic liver structure and metabolic zonnation were preserved. Expression profiling and pathway analysis depicted four master processes, all with response peaking at 24 hours, and all but one decreasing towards 72h. Changes in gene expression were compatible with cellular energy deficiency, and metabolic adaptations were directed at enhanced glucose production, stimulation of lipid catabolism and ketone body synthesis, and strongly augmented ATP production. Consequently, the expression of genes involved in oxidative and endoplasmic reticulum stress response was increased. In addition, urea cycle genes were strongly upregulated during whole duration of fasting, in spite no obvious increase in amino-acid catabolism. Major physiological change upon continued fasting was restoration of glycogen reserves, but with reverse localization, demonstrating utilization of different glycogenic precursor compared to the fed controls. Conclusion; The changes in liver gene expression indicate a rapid onset of generating glucose and ketone bodies during short, and a return to near normal situation in prolonged fasting. The reason apparently lies in glycogen repletion, due to late fasting glucose production by (gut and) kidney. Experiment Overall Design: Male FVB mice (Charles River, Maastricht, The Netherlands) were housed at 20-22°C, 50-60% humidity, a 12 hours light/dark cycle, and food and water ad libitum. At 6 weeks of age, mice were fasted by removing chow for up to 72 hours before sacrifice (n = 6 per group). All animals were sacrificed between 9:00 and 10:00 a.m. by cervical dislocation. The liver was removed quickly, weighed, snap-frozen in liquid N2, and stored at -80°C. Total intestinal RNA was extracted from frozen tissue using TRIzol (Invitrogen), followed by a cleanup through a RNeasy column (Qiagen). The quality of RNA was assessed with the RNA 6000 Nano LabChip® Kit in an Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, USA). The 60-mer Mouse Development (22K) Oligo Microarray G4120A (Agilent) was used. Three arrays per experimental condition were used. Per microarray, 20 μg mRNA, pooled from 2 livers, was reverse transcribed with Cy3-labelled dCTP (Perkin Elmer, Boston, USA), using the Agilent Fluorescent Direct Label Kit. Cy5-labeled cDNA produced from RNA pooled from livers of 6 fed animals served as the common reference across all arrays. Hybridized cDNAs were detected with Agilentâ??s dual-laser microarray slide scanner. The data were retrieved with Agilentâ??s Feature Extraction software 6.1.1.
2008-11-21 | E-GEOD-10653 | biostudies-arrayexpress