Critical roles for DNA methylation in embryonic development are well established, but less is known about the roles of DNA methylation during trophoblast development, the extraembryonic lineage that gives rise to the placenta. Here we dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b-null trophoblast. We find that most gene deregulation is explained by an erasure of maternal methylation in the oocyte, but partially independent of loss of imprinting of the trophoblast-essential Ascl2 gene. Our results reveal that maternal DNA methylation controls multiple differentiation and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. Overall design: mRNA-seq and WGBS-seq of maternal Dnmt3a/3b-null trophoblast; mRNA-seq of maternal Ascl2 KO trophoblast
Maternal DNA Methylation Regulates Early Trophoblast Development.
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View SamplesWe have investigated the effects of cigarette smoke exposure in three different strains of mice. DBA/2 and C57Bl/6J are susceptible to smoke and develop different lung changes in response to chronic exposure, while ICR mice are resistant to smoke and do not develop emphysema. The present study was carried out to determine early changes in the gene expression profile of mice exposed to cigarette smoke with either a susceptible or resistant phenotype.
Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke.
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View SamplesCultured epidermal keratinocytes treated with OsM 1, 4, 24 & 48hrs, and Skinethic epidermal substitutes treated 1, 4, 24, 48h & 7days, each with untreated control
Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.
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View SamplesThis is Rembrandt gene expression data (Affymetrix HG-U133Plus2).
Rembrandt: helping personalized medicine become a reality through integrative translational research.
Specimen part, Disease, Disease stage
View SamplesCTNNB1 is the most frequently mutated gene in hepatocellular carcinoma (HCC). However, its clinical relevance remains controversial. We determined an evolutionarily conserved -catenin signature by comparative analysis of gene expression data from human HCC and a mouse model (GSE43628). We generated gene expression data from the tumors of 88 HCC patients who underwent surgical resection as the primary treatment. We used these gene expression data to develop a new prognostification model for prognosis of HCC after surgery.
Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesIn this placebo-controlled randomized controlled trial, we tested whether remote ischemic preconditioning (RIPC) elicited by four 5-minute cycles of 300 mmHg of cuff inflation/deflation of the lower limb would reduce myocardial necrosis in isoflurane-anesthetized patients undergoing on-pump coronary artery bypass graft surgery. Secondary outcomes were the perioperative release of the biomarkers NTproBNP, hsCRP, S100, atrial transcriptional profiles, and short- and long-term clinical outcomes. RIPC with concomitantly applied isoflurane did not affect the release of biomarkers or clinical outcome. NTproBNP release correlated with isoflurane- but not RIPC-induced transcriptional changes.
Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection?
Specimen part, Treatment
View SamplesExpression profiling of hepatocytes-derived ductal cells with properties intermediate between mature hepatocytes and cholangiocytes Overall design: Chimeric adult mice were generated where mature hepatocytes were marked with a fluorescent red marker. Chronic injury was induced for ~6weeks and three cell types were isolated by FACS (Influx, BD) for expression analysis by RNAseq based on cell surface phenotype and origin: hepatocytes (n=3), hepatocyte-derived oval cells (1c3+, n=5), and cholangiocyte-derived oval cells (1c3+, n=5).
Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes.
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View SamplesCTNNB1 is the most frequently mutated gene in hepatocellular carcinoma (HCC). However, its clinical relevance remains controversial. We determined an evolutionarily conserved -catenin signature by comparative analysis of gene expression data from human HCC (GSE43619) and a mouse model.
Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.
Specimen part
View SamplesFumarylacetoacetate hydrolase (Fah), the last enzyme of the tyrosine degradation pathway, is specifically expressed in hepatocytes in the liver. Loss of Fah leads to liver failure in mice within 6-8 weeks. This can be prevented by blocking tyrosine degradation upstream of Fah with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC). Here, we investigate the impact of p21 on global gene expression in Fah deficiency.
Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis.
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View SamplesObservational studies in human suggest involvement of vitamin A/retinoic acid (RA) signaling in the regulation of airway smooth muscle (ASM) function, but the precise mechanisms by which RA impacts ASM phenotype is not clear. Here, we generated trascriptional profiles from two different models of RA-sufficient and RA-deficient mouse ASM in order to determine the molecular targets of RA in ASM (VAS/VAD, CTR/BMS)
Retinoic acid signaling is essential for airway smooth muscle homeostasis.
Specimen part
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