Preeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We recently identified five clusters of placentas within a large gene expression microarray dataset (N=330, GSE75010), of which four contained a substantial number of PE samples. However, while transcriptional analysis of placentas can subtype patients, we hypothesized that the addition of epigenetic information should reveal gene regulatory mechanisms behind the distinct PE pathologies. We, therefore, subjected 48 of our samples to Infinium Human Methylation 450K arrays and investigated relationships between the gene expression and DNA methylation data.
Epigenetic regulation of placental gene expression in transcriptional subtypes of preeclampsia.
Sex, Specimen part, Disease
View SamplesPreeclampsia (PE) is a complex, heterogeneous disorder of pregnancy, demonstrating considerable variability in observed maternal symptoms and fetal outcomes. We hypothesized that this heterogeneity is due to the existence of multiple molecular forms of PE. To address our hypothesis, we created a large (N=330) human placental microarray data set consisting of seven previously published studies (GSE30186, GSE10588, GSE24129, GSE25906, GSE43942, GSE4707, and GSE44711) and 157 highly annotated samples from a BioBank (below).
Unsupervised Placental Gene Expression Profiling Identifies Clinically Relevant Subclasses of Human Preeclampsia.
Specimen part, Disease
View SamplesFetal growth restriction (FGR) is a heterogeneous disorder of pregnancy associated with pathologically low fetal and neonatal weights. We hypothesized that FGR consists of multiple placental subtypes, similar to what we have observed in preeclampsia. To address this hypothesis, we assembled a fetal growth-focused human placental microarray data set (N=97) consisting of 20 new normotensive suspected FGR samples (below), in addition to term controls (N=26) and hypertensive suspected FGR samples (N=51) from GSE75010.
Placental transcriptional and histologic subtypes of normotensive fetal growth restriction are comparable to preeclampsia.
Specimen part
View SamplesWe aimed to identify genes that are regulated at downstream of FGFR1/KLB receptor complex in brown adiposetissues of adult male mice on high fat diet by injecting anti-FGFR1/KLB agonisticantibody or human FGF21.
Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex.
Specimen part
View SamplesWe elucidate a neurological syndrome affecting both the PNS and CNS defined by CLP1 mutations that impair tRNA splicing Overall design: Identification and biochemical characterization of mutant CLP1 in human patients
Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.
No sample metadata fields
View SamplesNormal erythropoiesis requires a critical balance between proapoptotic and antipaoptotic pathways. Bcl-xl, an antiapoptotic protein is induced at end-stages of differentiation of erythroid precursors in response to erythropoietin. The details of the proapoptotic pathway and the critical proapoptotic proteins inhibited by Bcl-xl in erythropoiesis are not well understood. We employed gene targeting to ablate Nix, a proapoptotic BH3-domain only Bcl2 family protein, which is known to be transcriptionally induced during erythropoiesis. Nix null mice exhibited reticulocytosis and thrombocytosis in the peripheral blood; and profound splenomegaly with erythroblastosis in the spleen and bone marrow despite normal erythropoietin levels and blood oxygen tension. In vivo apoptosis was diminished in erythroblast precursors from Nix null spleens. To define the molecular consequences of Nix ablation on apoptosis and erythropoiesis, we conducted a detailed comparative analysis of gene expression in spleens from 8 week old Nix null mice and wild type controls. Of 45,101 genes analyzed, 514 were significantly upregulated and 386 down-regulated in Nix-/- splenocytes. Functional cluster analysis delineated the ten most highly regulated gene sets, revealing increased levels of cell cycle and erythroid genes, with decreased levels of cell death and B-cell genes.
Unrestrained erythroblast development in Nix-/- mice reveals a mechanism for apoptotic modulation of erythropoiesis.
No sample metadata fields
View SamplesAnalysis of a SigX knockout mutant of Pseudomonas aeruginosa H103 strain in minimal medium with glucose as carbon source (M9G).
The extra-cytoplasmic function sigma factor sigX modulates biofilm and virulence-related properties in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesWistar rats, purchased from BRL (Fullinsdorf/BL, Switzerland), and WBN/Kob rats, purchased from SLC Inc. (Shizuoka, Japan), were specific pathogen-free. Rats were housed in groups of maximally 4 instandard cages (1,820 cm2 bottom area) and kept in our animal facility for various time periods between 1 week and 36 weeks (free access to standard rat chow and water; specific pathogen-free conditions; 20 degree C; day/night cycle simulated by artificial lighting of 50 lx from 7 a.m. to 7 p.m., dimmed in the remaining hours to almost complete darkness; air humidity 50 to 60%). Prior to surgery or sacrifice, the rats were fasted overnight (16 to18 h) with free access to water. All manipulations conformed with the Swiss Federal Guidelines on Animal Experiments and were approved by the local ethics committee.
Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis.
Sex, Age, Specimen part, Time
View SamplesOral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology.
A YAP/TAZ-Regulated Molecular Signature Is Associated with Oral Squamous Cell Carcinoma.
Cell line, Treatment
View SamplesObjective:
Gene expression analysis in absence epilepsy using a monozygotic twin design.
Sex
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