This SuperSeries is composed of the SubSeries listed below.
Waterpipe smoking induces epigenetic changes in the small airway epithelium.
Specimen part
View SamplesWaterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use water-pipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.
Waterpipe smoking induces epigenetic changes in the small airway epithelium.
Specimen part
View SamplesStandardization of MSC manufacturing is urgently needed to facilitate comparison of clinical trial results. Here, we compare gene expression of MSC generated by the adaptation of a proprietary method for isolation and cultivation of a specific umbilical cord tissue-derived population of Mesenchymal Stromal Cells (MSCs)
Towards an advanced therapy medicinal product based on mesenchymal stromal cells isolated from the umbilical cord tissue: quality and safety data.
No sample metadata fields
View SamplesTranscriptome analysis of hindlimb muscles from dystrophic mice
Comparative transcriptome analysis of muscular dystrophy models Large(myd), Dmd(mdx)/Large(myd) and Dmd(mdx): what makes them different?
Sex, Specimen part
View SamplesHow the various cell-types of the body achieve their specific shapes is fundamentally unknown. Here, we explore this issue by identifying genes involved in the elaboration of the complex, yet conserved, cellular morphology of Müller glial (MG) cells in the retina. Using genomic based strategies in zebrafish, we found more than 40 candidate genes involved in specific aspects of MG morphogenesis. The successive steps of cell morphogenesis correlate with the timing of the expression of cohorts of inter-related genes that have roles in generating the particular anatomical features of these cells, suggesting that a sequence of genetic regulomes govern stepwise cellular morphogenesis in this system. Overall design: 12 samples with three replicates each are provided. GFAP:GFP positive and negative cells were FAC sorted from wild type animals from each developmental stage
Genetic control of cellular morphogenesis in Müller glia.
Specimen part, Subject
View SamplesThe pattern of gene transcription in Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. To investigate the requirement of PKA for glucose control of gene expression, we have analyzed global transcription in strains devoid of PKA activity. In S. cerevisiae three genes, TPK1, TPK2, TPK3, encode catalytic subunits of PKA and the triple mutant tpk1 tpk2 tpk3 is unviable. We have worked, therefore, with two strains, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4, that bear suppressor mutations,. We have identified different classes of genes that can be induced, or repressed, by glucose in the absence of PKA. Among these genes, some are also controlled by a redundant signalling pathway involving PKA activation, while others do not respond to an increase in cAMP concentration. On the other hand, among genes which do not respond to glucose in the absence of PKA, some show a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways.
Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A.
Treatment, Time
View SamplesValidation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer.
Intrahepatic cholangiocarcinoma progression: prognostic factors and basic mechanisms.
Sex, Specimen part
View SamplesPolybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in a variety of commercial and household products. They have been detected in the environment and accumulate in mammalian tissues and fluids. PBDE toxicity is thought to be associated with endocrine disruption, developmental neurotoxicity and changes in fetal development. Although humans are exposed to PBDEs, our knowledge of the effects of PBDE metabolites on human cells with respect to health risk is insufficient. Two hydroxylated PBDEs (OH-PBDEs), 2-OH-BDE47 and 2-OH-BDE85, were investigated for their effects on cell viability/proliferation, DNA damage, cell cycle distribution and gene expression profiling in H295R adrenocortical carcinoma cells. We show that the two agents are cytotoxic in a dose-dependent manner only at micromolar concentrations, with 2-OH-BDE85 being more toxic than 2-OH-BDE47. However, no DNA damage was observed for either chemical, suggesting that the biological effects of OH-PBDEs occur primarily via non-genotoxic routes. Furthermore, no evidence of aryl hydrocarbon receptor (AHR)-mediated, dioxin-like toxicity was observed. Instead, we report that a micromolar concentration of OH-PBDEs induces transcriptional changes associated with endoplasmic reticulum stress and the unfolded protein response. We discuss whether OH-PBDE bioaccumulation could result in impairment of the adrenocortical secretory function.
Cytotoxicity and gene expression profiling of two hydroxylated polybrominated diphenyl ethers in human H295R adrenocortical carcinoma cells.
No sample metadata fields
View SamplesAberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. Overall design: RNA-seq of SETD2 mutant and wild-type ccRCC cell lines.
Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma.
No sample metadata fields
View SamplesIn humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated when the germ cell loss begins and whether it is caused by dysgenetic fetal development of the testes. We investigated a series of fetal KS testis tissue samples and found a marked reduction in MAGE-A4-positive pre-spermatogonia in the developing KS gonads compared to controls, indicating a failure of the gonocytes to differentiate into pre-spermatogonia. Transcriptome analysis by RNA sequencing of formalin-fixed and paraffin embedded gonads originating from 4 fetal KS samples and 5 age- and cellularity-matched controls revealed 211 differentially expressed transcripts in the fetal KS testis. We found a significant enrichment of upregulated X-chromosomal transcripts and validated the expression of the pseudoautosomal region 1 (PAR1) gene, AKAP17A. Moreover, we found enrichment of long non-coding RNAs in the KS testes (e.g. LINC01569 and RP11-485F13.1). In conclusion, our data indicates that the testicular phenotype observed among adult men with KS is initiated already in fetal life by failure of the gonocyte differentiation into pre-spermatogonia, which could be due to aberrant expression of long non-coding RNAs. Overall design: Includes a total of 9 samples. 4 fetal Klinefelter and 5 age-matched controls testis samples
Transcriptome profiling of fetal Klinefelter testis tissue reveals a possible involvement of long non-coding RNAs in gonocyte maturation.
Subject
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