This SuperSeries is composed of the SubSeries listed below.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Specimen part, Disease, Disease stage, Subject
View SamplesTo acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Subject
View SamplesTo acquire a better understanding of the molecular pathogenesis of hidradenitis suppurativa (HS), we performed mRNA microarray studies to compare whole blood gene expression of HS patients to that of healthy normal subjects.
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Specimen part, Disease, Disease stage, Subject
View SamplesOur goal was to demonstrate the similarity between the original keratinocytes and iPSC-derived keratinocytes from the same individual
Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa.
Specimen part
View SamplesTo provide further insight about the effects of prolonged Ezh2 inhibition in glioblastoma using preclinical mouse models and doxycycline-inducible shRNAs that mimic the effects of a selective EZH2 inhibitor. We demonstrate that prolonged Ezh2-depletion causes a robust switch in cell fate, including significantly enhanced proliferation and DNA damage repair and activation of part of the pluripotency network, resulting in altered tumor cell identity and tumor progression. Overall design: SVZ derived neural stem cells (NSCs) were isolated from 7 days old p53;Ink4a/Arf;Krasv12;LucR compound conditional mice and cultured in NSC specific serum-free medium supplemented with 20ng/ml of both EGF and bFGF (R&D systems). NSCs were grown adhesion-free for the first passages to eliminate non-sphere-forming cells. Next, cells were grown adherent on poly-L-Ornithine and Laminin plates and three times infected with lentiviral CMV-Cre. These floxed, tumorigenic cells are further referred as glioma initiating cells (GICs). Next, GICs were infected with a tet-inducible, doxycycline-responsive short hairpin construct (FH1-tUTG-shEzh2). After FACS sorting for GFP, GICs were injected intracranial in NOD-SCID mice and treated with or without doxycycline in the drinking water
Prolonged Ezh2 Depletion in Glioblastoma Causes a Robust Switch in Cell Fate Resulting in Tumor Progression.
No sample metadata fields
View SamplesThe mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown.
Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension.
Sex, Specimen part
View SamplesHeterozygous mutations in the transcription factor GATA3 are identified in 10-15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice. Overall design: RNAseq data of T47D cells expressing HA-tagged wild-type GATA3 (HA_GATA3_wt) or one of two truncated variants (HA_GATA3_TR1 and HA_GATA3_TR2).
GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice.
Specimen part, Cell line, Subject
View SamplesHIV-1 nucleoside reverse transcriptase inhibitor (NRTI) use is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to NRTIs has predominantly been assigned to mitochondrial polymerase-? inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS) production and their role in toxicity is unclear. In this study we show that short-term effects of these drugs, which are rarely discussed in the literature, include direct inhibition of the mitochondrial respiratory chain (MRC), decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC), which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure. Overall design: RNA-seq on Caenorhabditis elegans exposed to DMSO, 3''-azido-3''-deoxythymidine (zidovudine or AZT), 2'',3''-didehydro-2'',3''-deoxythymidine (stavudine or d4T), 3''-deoxy-3''-fluorothymidine (alovudine or FLT) or untreated control after 24 or 72 hours of exposure.
Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.
Specimen part, Subject
View SamplesResponse to allergen was studied in epithelial cells derived from allergic pantients and from healthy controls. Cells were cultured after isolation from a nasal biopsy. Cells were exposed to Housed dust mite or vessel (saline)
Primary nasal epithelium exposed to house dust mite extract shows activated expression in allergic individuals.
No sample metadata fields
View SamplesThe present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest-Observed-Adverse-Effect-Level (LOAEL) or at a two- or three-fold lower concentration individually or in binary or ternary mixtures. The compounds had strong antagonistic effects on each others gene expression changes, which included several genes encoding Phase I and II metabolizing enzymes. On the other hand, the mixtures affected the expression of “novel” genes that were not or little affected by the individual compounds. Based on gene expression changes, the three compounds exhibited a synergistic interaction at the LOAEL in the liver and both at the sub-LOAEL and LOAEL in the kidney. Many of the genes induced by mixtures but not by single compounds, such as Id2, Nr2f6, Tnfrsf1a, Ccng1, Mdm2 and Nfkb1 in the liver, are known to affect cellular proliferation, apoptosis and function. This indicates a shift from compound specific response on exposure to individual compounds to a more generic stress response to mixtures. Most of the effects on cell viability as concluded from transcriptomics were not detected by classical toxicological research illustrating the difference in sensitivity of these techniques. These results emphasize the benefit of applying toxicogenomics in mixture interaction studies, which yields biomarkers for joint toxicity and eventually can result in an interaction model for most known toxins.
Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat.
Sex, Age, Specimen part, Treatment, Compound
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