Liver tissue from the "Four Core Genotype" treated group C57BL/6J mice versus pool C57BL/6J mice of chow diet Liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Leslie Ingram-drake
PROVIDER: E-GEOD-13264 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks.
van Nas Atila A Guhathakurta Debraj D Wang Susanna S SS Yehya Nadir N Horvath Steve S Zhang Bin B Ingram-Drake Leslie L Chaudhuri Gautam G Schadt Eric E EE Drake Thomas A TA Arnold Arthur P AP Lusis Aldons J AJ
Endocrinology 20081030 3
We previously used high-density expression arrays to interrogate a genetic cross between strains C3H/HeJ and C57BL/6J and observed thousands of differences in gene expression between sexes. We now report analyses of the molecular basis of these sex differences and of the effects of sex on gene expression networks. We analyzed liver gene expression of hormone-treated gonadectomized mice as well as XX male and XY female mice. Differences in gene expression resulted in large part from acute effects ...[more]
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Project description:The purpose of this experiment was to determine the expression traits in animals of inbred strain C57BL/6J, treated with gonadal hormones. (N=40, 20 males and 20 females). Liver tissue from the hormone treated group consists of 40 female and male C57BL/6J mice fed a chow diet containing 4% fat (Ralston-Purina Co., St. Louis, MO) until 8 weeks of age and then were gonadectomized at 8 weeks of life, implanted with hormone pellets at 12 weeks, and sacrificed at 14 weeks. Male and female mice of the hormone treated groups received subcutaneous implants of either 0.5 mg estradiol (E2) pellet (plasma yield of 300 picogram/ml) or a 5 mg dihydrotestosterone (DHT) pellet (plasma yield of 1-2 nanogram/ml), designed to release over 21 days, (Innovative Research of America, 17B-estradiol: Cat. No. E-121 0.5mg/pellet, 5a-dihydrotestosterone: Cat. No. A-16). Control mice were treated with the placebo pellet (Innovative Research of America, placebo: Cat. No. C-111). At 14 weeks mice were sacrificed, after a 12-hour fast, Liver tissue were dissected and flash frozen in LN2 and stored at -80°C. All sample were compared to a common pool created from equal portions of RNA from each of the samples. Keywords=hormone treated Mouse liver Tissue
2010-06-24 | E-GEOD-13265 | biostudies-arrayexpress
Project description:To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1,000 patients undergoing Roux-en-y gastric bypass and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than one hundred thousand gene expression traits representing four metabolically relevant tissues; liver, omental adipose, subcutaneous adipose and stomach. We successfully identified 24,531 eSNPs corresponding to ~10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high quality disease map for each tissue in morbidly obese patients to not only inform genetic associations indentified in this cohort, but in previously published genome wide association studies as well. eSNPs and gene co-expression modules identification in morbidly obese patients represent a great resource that will aid in elucidating the key networks associated with morbid obesity, response to RYGB and disease as a whole. Keywords: Tissue profiling in a human cohort. Liver tissue was collected from patients at the time of RYGB surgery at Massachusetts General Hospital between 2000 and 2007. Samples were collected in RNAlater (Ambion/Applied Biosystems), stored at -80° and shipped to Rosetta Inpharmatics Gene Expression Laboratory Seattle, WA for extraction, amplification, labeling, and microarray processing. Samples processed ranged in size from 100-200mg. Total RNA extracted from liver was converted to fluorescently labeled cRNA that was hybridized to custom 44K DNA oligonucleotide microarrays manufactured by Agilent Technologies as described previously (Hughes et al. 2001; Schadt et al. 2008). Successful gene expression profiling results were collected from 651 liver samples.
2011-04-01 | E-GEOD-24293 | biostudies-arrayexpress
Project description:Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, reflecting the need for a better understanding of hepatocarcinogenesis. In this study, we examined the genome-wide expression profiles of both miRNAs and mRNAs from paired tumor and adjacent non-tumor tissues from a cohort of 96 HCC patients in Hong Kong where hepatitis B virus (HBV) is endemic. The comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that it is an important regulator for normal mitochondrial metabolism. A decreased level of miR-122 leads to an increase in expression of miR-122 seed-matched genes, a loss of mitochondrial metabolic function, and a decrease in the expression of many miR-122 secondary targets. These secondary targets are prognostic markers for HCC patients. Transcriptome profiling data from an additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. To test the HCC findings in normal mouse liver, we used an antagomir against miR-122 and identified altered gene expression profiling by microarray analysis in mouse in vivo experiments. The mouse data recapitulated the human HCC findings. Our anti-miR122 data further provided a direct link between increases in the mRNA levels of miR-122 controlled genes and impairments of mitochondrial metabolism. In summary, we find miR-122 loss may be detrimental to mitochondrial-related metabolisms in sustaining critical liver function and contribute to the morbidity and mortality of liver cancer patients. Mouse liver profiling: In one treatment regimen, four animals were given four doses of 100mg ASO/kg body weight, administered every other day, and sacrificed one day after the last dose. Four animals treated for four weeks were treated twice weekly with 50mg ASO/kg body weight, and sacrificed two days after the last dose. Mice were sacrificed in the morning, and liver was removed for further analysis. Samples from oligonucleotide-treated mice were referenced against samples from saline-treated mice in fluor-reversed pairs. Human liver profiling: For human HCC patient samples, 192 samples -- 96 resected tumor and 96 adjacent non-tumor liver tissues -- were collected from 96 patients who had undergone hepatectomy for curative treatment of HCC at Queen Mary Hospital, Pokfulam, Hong Kong between 1990 and 2007. Informed consents were obtained from patients regarding the use of the liver specimens for research. Samples were hybridized to Affymetrix arrays for mRNA profiling and were analyzed by quantitative PCR for microRNA profiling.
2010-06-09 | E-GEOD-22058 | biostudies-arrayexpress
Project description:Mice overexpressing reverse tetracycline-transactivator (rtTA) exhibited all four sequelae of metabolic syndrome (visceral obesity insulin resistance, dyslipidemia, and hypertension), a pro-inflammatory state and marked hepatic steatosis. Gene expression profiling of the adipose tissue, muscle and liver revealed changes in gene expression of key factors involved in lipid metabolism, insulin resistance, and inflammation. Liver, epididymal White Adipose Tissue, kidney cortex, kidney medulla and muscle from wild type (FVB mice, Taconic Farms) and rtTA overexpressing mice (line 6) were profiled in Merck/Agilent mouse 44k v1.0 arrays. For each tissue, a reference pool was used composed of total RNA from that tissue obtained from FVB mice. Channel 1 is the reference pool, channel 2 is the sample.
2011-06-30 | E-GEOD-23302 | biostudies-arrayexpress
Project description:We profiled gene expression in liver tissue from F2 progeny from a cross between the outbred M16 (selectively bred for rapid weight gain) and ICR (control) mouse strains. We developed a framework for reconstructing tissue-to-tissue coexpression networks between genes in hypothalamus, liver or liver tissues that are independent of networks constructed from single tissue analyses. The subnetworks we identify as specific to tissue-to-tissue interactions associate with multiple obesity-relevant biological functions like circadian rhythm, energy balance, stress response, or immune response. Keywords: Tissue profiling in a mouse F2 cross. We analyzed 302 liver samples.
2009-10-25 | E-GEOD-13752 | biostudies-arrayexpress
Project description:To identify the genes and pathways that underlie cardiovascular and metabolic phenotypes we performed an integrated analysis of a mouse C57BL/6J x A/J F2 (B6AF2) cross by relating genome-wide gene expression data from adipose, kidney, and liver tissues to physiological endpoints measured in the population. We have identified a large number of trait QTLs including loci driving variation in cardiac function on chromosomes 2 and 6 and a hotspot for adiposity, energy metabolism, and glucose traits on chromosome 8. Integration of adipose gene expression data identified a core set of genes that drive the chromosome 8 adiposity QTL. This chromosome 8 trans eQTL signature contains genes associated with mitochondrial function and oxidative phosphorylation and maps to a subnetwork with conserved function in humans that was previously implicated in human obesity. In addition, human eSNPs corresponding to orthologous genes from the signature show enrichment for association to type II diabetes in the DIAGRAM cohort, supporting the idea that the chromosome 8 locus perturbs a molecular network that in humans senses variations in DNA and in turn affects metabolic disease risk. We functionally validate predictions from this approach by demonstrating metabolic phenotypes in knockout mice for three genes from the trans eQTL signature, Akr1b8, Emr1, and Rgs2. In addition we show that the transcriptional signatures for knockout of two of these genes, Akr1b8 and Rgs2, map to the F2 network modules associated with the chromosome 8 trans eQTL signature and that these modules are in turn very significantly correlated with adiposity in the F2 population. Overall this study demonstrates how integrating gene expression data with QTL analysis in a network-based framework can aid in the elucidation of the molecular drivers of disease that can be translated from mice to humans. An F2 population was derived from a C57BL/6J x A/J mouse cross (B6AF2) and tissues were collected in 360 male and female progeny for microarray analysis. RNA extraction, probe preparation, and array hybridizations were all carried out at the Rosetta Inpharmatics Gene Expression Laboratory (Seattle, WA). Mouse tissues (gonadal adipose, kidney medulla, kidney cortex, hypothalamus) were pulverized prior to homogenization in a solution of GITC/BME (1:50 ratio) using a Covaris S2 cryo-prep (Covaris, Inc, Woburn, MA), followed by addition of a TRIzol water solution (4:1 ratio). 100% Chloroform was added to the TRIzol/GITC lysate (1:5 ratio) to facilitate separation of the organic and aqueous components using the phaselock (Eppendorf) system. The aqueous supernatant was further purified using a Promega SV-96 total RNA kit (Promega, Madison, WI), incorporating a DNase treatment. Total RNA samples were assayed for quality using an Agilent Bioanalyzer (Agilent Technologies, Santa Clara, CA) and for yield using Ribogreen (Ambion, Austin, TX) metrics prior to amplification. All samples, with the exception of kidney medulla, were amplified and labeled using a custom automated version of a 5 µg RT/IVT protocol and hybridizations to custom Agilent microarrays were performed as described [58]. The custom ink-jet microarrays used in this study were manufactured by Agilent Technologies and consisted of 4,732 control probes and 39,558 non-control oligonucleotides derived from mouse Unigene clusters, combined with RefSeq sequences and RIKEN full-length cDNA clones. For each individual animal tissue sample, labeled complementary RNA (cRNA) was hybridized against a pool of labeled cRNAs constructed from equal aliquots of RNA for that specific tissue from at least 200 individuals.
2011-01-13 | E-GEOD-25506 | biostudies-arrayexpress
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2011-02-02 | E-GEOD-20903 | biostudies-arrayexpress
Project description:To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1,000 patients undergoing Roux-en-y gastric bypass and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than one hundred thousand gene expression traits representing four metabolically relevant tissues; liver, subcutaneous adipose, omental adipose and stomach. We successfully identified 24,531 eSNPs corresponding to ~10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high quality disease map for each tissue in morbidly obese patients to not only inform genetic associations indentified in this cohort, but in previously published genome wide association studies as well. eSNPs and gene co-expression modules identification in morbidly obese patients represent a great resource that will aid in elucidating the key networks associated with morbid obesity, response to RYGB and disease as a whole. Keywords: Tissue profiling in a human cohort. Subcutaneous adipose tissue was collected from patients at the time of RYGB surgery at Massachusetts General Hospital between 2000 and 2007. Samples were collected in RNAlater (Ambion/Applied Biosystems), stored at -80° and shipped to Rosetta Inpharmatics Gene Expression Laboratory Seattle, WA for extraction, amplification, labeling, and microarray processing. Samples processed ranged in size from 100-200mg. Total RNA extracted from subcutaneous adipose was converted to fluorescently labeled cRNA that was hybridized to custom 44K DNA oligonucleotide microarrays manufactured by Agilent Technologies as described previously (Hughes et al. 2001; Schadt et al. 2008). Successful gene expression profiling results were collected from 701 subcutaneous adipose samples.
2011-04-01 | E-GEOD-24297 | biostudies-arrayexpress
Project description:To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1,000 patients undergoing Roux-en-y gastric bypass and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than one hundred thousand gene expression traits representing four metabolically relevant tissues; liver, omental adipose, subcutaneous adipose and stomach. We successfully identified 24,531 eSNPs corresponding to ~10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high quality disease map for each tissue in morbidly obese patients to not only inform genetic associations indentified in this cohort, but in previously published genome wide association studies as well. eSNPs and gene co-expression modules identification in morbidly obese patients represent a great resource that will aid in elucidating the key networks associated with morbid obesity, response to RYGB and disease as a whole. Keywords: Tissue profiling in a human cohort. Omental adipose tissue was collected from patients at the time of RYGB surgery at Massachusetts General Hospital between 2000 and 2007. Samples were collected in RNAlater (Ambion/Applied Biosystems), stored at -80° and shipped to Rosetta Inpharmatics Gene Expression Laboratory Seattle, WA for extraction, amplification, labeling, and microarray processing. Samples processed ranged in size from 100-200mg. Total RNA extracted from omental adipose was converted to fluorescently labeled cRNA that was hybridized to custom 44K DNA oligonucleotide microarrays manufactured by Agilent Technologies as described previously (Hughes et al. 2001; Schadt et al. 2008). Successful gene expression profiling results were collected from 848 omental adipose samples.
2011-04-01 | E-GEOD-24294 | biostudies-arrayexpress
Project description:Background and Rationale: Factor VII activating protease (FSAP) is a circulating serine protease produced in the liver. A single nucleotide polymorphism (G534E, Marburg I, MI-SNP) in the gene encoding FSAP (HABP2) leads to lower enzymatic activity and is associated with enhanced liver fibrosis. FSAP is activated by damaged cells and its substrates include growth factors and haemostasis proteins. We have investigated the progression of liver fibrosis in FSAP deficient mice. Results: Wild type (WT) or FSAP-/- mice were subjected to bile duct ligation (BDL) and assessment of liver fibrosis. FSAP-/- mice showed enhanced liver fibrosis and accumulation of extracellular matrix as determined by Sirius Red staining and hydroxyproline content. FSAP deficient mice exhibited stronger injury as determined by higher necrosis in the liver and circulating liver enzymes. This correlated with expression of markers like M-NM-1-smooth muscle actin, collagen and fibronectin that are markers of stellate cell activation. FSAP-deficient mice exhibited higher expression of PDGF-BB as well as PDGFRM-NM-2 that are strong activators of liver fibrosis. In order to gain more insight into this difference microarray analysis was performed and the pattern of gene expression in WT vs. FSAP-/- mice would indicate that FSAP modulates the inflammatory /immune system. Conclusions: The results with FSAP-/- mice correlates with the human situation where lower FSAP activity, due to the MI SNP, is associated with enhanced liver fibrosis. This strengthens the concept that FSAP is a M-bM-^@M-^\protective factorM-bM-^@M-^] in liver fibrosis. A probable mechanism for this effect is likely to be related to the role of FSAP in the regulation of fibrosis/ inflammation-related processes n the liver. The dataset comprises 12 samples divided into four sample groups each representing a certain treatment group.
2012-09-19 | E-GEOD-36066 | biostudies-arrayexpress