Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcriptome expression profile of tissue from BAHD1+/+ (WT) and BAHD1-/- (KO) mice

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: HÃ©lÃ¨ne Bierne

PROVIDER: E-GEOD-53443 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

Lakisic Goran G Lebreton Alice A Pourpre Renaud R Wendling Olivia O Libertini Emanuele E Radford Elizabeth J EJ Le Guillou Morwenna M Champy Marie-France MF Wattenhofer-Donzé Marie M Soubigou Guillaume G Ait-Si-Ali Slimane S Feunteun Jean J Sorg Tania T Coppée Jean-Yves JY Ferguson-Smith Anne C AC Cossart Pascale P Bierne Hélène H

PLoS genetics 20160303 3

BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome ...[more]

PMID: 26938916

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Project description:A data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix). Background: Ovarian cancer is the most lethal gynecologic cancer in the United States. If caught in early stages, patient survival rate can reach 94%, when diagnosed at late stages survival rates drop to 28%. Correct diagnosis depends on the presence of definite symptoms: while ~90% of diagnosed ovarian cancers have symptoms, they tend to be unfocused and subacute. A definitive and early molecular signature of disease is thus desired. To further progress towards this goal, we present an Affymetrix™ human exon array data set measuring ovarian tumor expression, assembled using best practices. Method: Samples were collected from patients with benign and malignant (type II) serous ovarian surface epithelial-stromal tumors. Normal epithelium, tumor, stroma adjacent to tumor, and distal stroma were selected based on histopathology, and isolated using laser capture microdissection. Nugen products were used to perform random-primed mRNA amplification procedures (for full transcript capture) before hybridization to Affymetrix exon chips. Tumor expression and paracrine signaling was assessed using GC-RMA and a two-way Model I ANOVA. Single enrichment ontological analysis and gene network construction were performed to guide inferences about biological context. Results: In total, across 50 microarrays, ~270 million measurements were obtained. Based on comparisons to known ovarian cancer properties as established in molecular genetics literature, the initial analysis presented emphasizes data quality. Major trends between sample classes included: apical surface and tight junction activity, mitotic activity, benign tumor suppression, epithelial-mesenchymal transitioning, tumor oncogene activity, and paracrine signaling. A list of differentially expressed transcripts has been produced to enable rapid comparisons with published biomarker lists, but it is expected that detailed alternative transcript analysis will refine these predictions. Conclusions: A data set of 50 arrays, from carefully dissected serous ovarian surface epithelial-stromal tumors, has been produced, from which high quality measurements were obtained. While relatively small in number, this represents an important addition to the community pool of ovarian tumor samples, and the chosen platform enables bridging between 3' expression and exome sequencing data sets. This represents a significant contribution to the ovarian cancer genetics community. A total of 50 human ovary samples were used in analysis: 23 tissue samples laser capture microdissected from an ovary with a benign serous tumor (specifically 4 normal epithelium samples, 5 tumor samples, 6 stroma samples adjacent to the tumor, and 8 stroma samples distal of the tumor), and 27 tissue samples laser capture microdissected from an ovary with a malignant serous tumor (specifically 5 normal epithelium samples, 8 tumor samples, 7 stroma samples adjacent to the tumor, and 7 stroma samples distal of the tumor). Additional cel files were provided which, although were used in the quality control of the data set, were not used in the final experimental analysis. 8 replicates are included as cel files (1 from each cohort previously listed). 14 cel files were also included which failed quality control. Although the replicate and failed cel files were not used in the final analysis, they may still be interesting in other research.

Project description:Gene-expression profiles of liver and hepatocellular carcinoma induced by diethylnitrosamine (DEN) in KLF6 +/- and wild type KLF6 mice. Inactivation of the KLF6 tumor suppressor is common in HCC due to hepatitis C virus (HCV), consistent with its anti-proliferative activity in HCC-derived cell lines and in hepatocytes of transgenic mice. We have evaluated the impact of KLF6 depletion on human HCC and experimental hepatocarcinogenesis. In patients with surgically resected HCC, those with significantly reduced tumor expression of KLF6 had a significantly decreased survival. We modeled this event in KLF6 +/- mice, which displayed significantly more tumorigenicity than KLF6 +/+ animals in response to the hepatic carcinogen DEN, associated with recapitulation of gene signatures in both surrounding tissue and tumors that are associated with aggressive human HCCs. In DNA microarrays, mdm2 mRNA expression was increased in tumors from KLF6 +/- compared to KLF6 +/+ mice, which was validated by realtime qPCR and Western blot in both human HCC and DEN-induced murine tumors. Moreover, chromosomal immunoprecipitation and co-transfection assays established the P2 intronic promoter of mdm2 as a bona fide transcriptional target repressed by KLF6. Whereas KLF6 over-expression in HCC cell lines led to reduced MDM2 levels and increased p53 protein and transcriptional activity, reduction in KLF6 by siRNA led to increased MDM2 and reduced p53. Our findings indicate that KLF6 deficiency contributes significantly to the carcinogenic milieu in human and murine HCC, and uncover a novel tumor suppressor activity of KLF6 in HCC, by linking its transcriptional repression of MDM2 to stabilization of p53. Keywords: Liver, Hepatocellular carcinoma, Expression array, Exon array, Affymetrix KLF6 +/- mice were previously generated by homologous recombination in which exon 2 was targeted using an 11-kb targeting construct, and replaced with neomycin/lacZ cassette. After selection with neomycin, the ES clones were injected into C57BL/6 mouse blastocysts and implanted into pseudo pregnant females; two lines of KLF6 +/- mice were generated from the resulting chimeric animals (Blood 107;1357, Oncogene 26;4428). Whereas KLF6 -/- mice are embryonic lethal, KLF6 +/- animals had no demonstrable abnormalities in the absence of any stressor. Male KLF6 +/- mice were bred with wild type C57BL/6 to generate mixed litters of KLF6 +/- and KLF6 +/+ animals. Progeny were genotyped using PCR-amplified tail DNA, using primers as previously described (Oncogene 26;4428). Amplified fragments were separated on a 2.5% agarose gel, revealing bands of ~200 bp (wild type KLF6) and ~100 bp (Neo), as expected. At 2 weeks of age, KLF6 +/+ and KLF6 +/- mice were injected intraperitoneally with either a single dose of diethyl nitrosamine (DEN), 5 µg/g body weight in 100 µl of saline, or vehicle alone. Vehicle and DEN-treated mice were maintained on standard chow, and then sacrificed 3, 6 or 9 months later. At the time of sacrifice the animals were weighed, and blood and liver samples were harvested for analysis and tumor quantification.

Dataset Information

Transcriptome expression profile of tissue from BAHD1+/+ (WT) and BAHD1-/- (KO) mice

Publications

Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

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