Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin (DMD) gene. The absence of dystrophin protein leads to progressive muscle weakness and wasting, disability and death. To establish a tailored large animal model of DMD, we deleted DMD exon 52 in male pig cells by gene targeting and generated offspring by nuclear transfer. DMD pigs exhibit absence of dystrophin in skeletal muscles, increased serum creatine kinase levels, progressive dystrophic changes of skeletal muscles, impaired mobility, muscle weakness, and a maximum life span of 3 months due to respiratory impairment. To address the accelerated development of muscular dystrophy in DMD pigs as compared to human patients, we performed a genome-wide transcriptome study of M. biceps femoris samples from 2-day-old and 3-month-old DMD and age-matched wild-type pigs. The transcriptome changes in 3-month-old DMD pigs were in good accordance with the findings of gene expression profiles in human DMD, reflecting the processes of degeneration, regeneration, inflammation, fibrosis, and impaired metabolic activity. The transcriptome profile of 2-day-old DMD pigs pointed towards increased protein and DNA catabolism, reduced extracellular matrix formation and cell proliferation and showed similarities with transcriptome changes induced by exercise injury in muscle. Our transcriptome studies provide new insights into congenital changes associated with dystrophin deficiency and secondary complications arising during postnatal development. Thus the DMD pig is a useful model to determine the hierarchy of physiological derangements in dystrophin-deficient muscle.
Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle.
Age, Specimen part
View SamplesRecent studies demonstrated that tumor cells with stem cell-like properties can be cultured from human glioblastomas by using conditions that select for the expansion of neural stem cells. We established glioblastoma stem-like (GS-) cell cultures from 9 different glioblastomas, 8 of which generated stably expandable cell lines. Analyzing GS-cell cultures, we discovered two clearly discernable phenotypes.
Glioblastoma-derived stem cell-enriched cultures form distinct subgroups according to molecular and phenotypic criteria.
No sample metadata fields
View SamplesWe compared a large panel of human glioblastoma stem-like (GS) cell lines, corresponding primary tumors and conventional glioma cell lines to identify cell lines that preserve the transcriptome of human glioblastomas most closely, thereby allowing identification of shared therapeutic targets.
A distinct subset of glioma cell lines with stem cell-like properties reflects the transcriptional phenotype of glioblastomas and overexpresses CXCR4 as therapeutic target.
No sample metadata fields
View SamplesAcetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.
A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.
Sex, Age, Specimen part
View SamplesThe aim of this study is to generate and validate biomarkers to stratify patients with Barretts esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barretts esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barretts esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort.
Wdr66 is a novel marker for risk stratification and involved in epithelial-mesenchymal transition of esophageal squamous cell carcinoma.
Specimen part
View SamplesMultiple sclerosis (MS) is a neurodegenerative disease with a presumed autoimmune component. Expression profiling in immune cells can therefore be used in order to identify genes and pathways involved in MS pathogenesis.
Systematic review of genome-wide expression studies in multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesPhloem-feeding pests cause extensive crop damage throughout the world yet little is understood about how plants perceive and defend themselves from these threats. The silverleaf whitefly (SLWF; Bemisia tabaci type B) is a good model for studying phloem-feeding insect-plant interactions as SLWF nymphs cause little wounding and have a long, continuous interaction with the plant. Using the Arabidopsis ATH1 GeneChip, the global responses to Silverleaf Whitefly 2nd instar feeding were examined.
Arabidopsis transcriptome changes in response to phloem-feeding silverleaf whitefly nymphs. Similarities and distinctions in responses to aphids.
Age
View SamplesGastric cancer can be divided in two major histological subtypes: diffuse and intestinal-type adenocarcinomas. Since both types diverge in many clinical and molecular characteristics, is widely accepted that both represent distinct disease entities that may benefit from different therapeutic approaches. The diffuse type is explicitly more invasive and affected patients possess extremely poor prognosis. Gene expression profiling studies identified numerous genes with differences in mRNA expression between the two types. However, little overlap of published gene lists exists forcing the need for further and more comprehensive analyses.
THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Otitis media impacts hundreds of mouse middle and inner ear genes.
Age, Specimen part, Treatment
View SamplesObjective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.
Otitis media impacts hundreds of mouse middle and inner ear genes.
Age, Specimen part, Treatment
View Samples