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GSE58867
Homo sapiens
43 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of TH17 cells redirected with chimeric antigen receptors (CAR) expressing various signaling domains (including CD28, 4-1BB and ICOS) after surrogate antigen stimulation.
Publication Title
ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease.
Publication Title
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bipolar disorder (BD) has an estimated heritability of about 80%. Different pathways and candidate genes may contribute to the pathogenesis of BD, but definite mechanisms are yet unresolved. In a previous study, we identified the single nucleotide polymorphism (SNP) rs4500567, located in the upstream region of Tetraspanin 8 (TSPAN8), to be associated with bipolar disorder (BD).
Publication Title
The regulation of tetraspanin 8 gene expression-A potential new mechanism in the pathogenesis of bipolar disorder.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 34 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Consumption of diets rich in fibers has been associated with several beneficial effects on gastrointestinal health. However, detailed studies on the molecular effects of fibers in colon are limited. In this study we investigated and compared the influence of five different fibers on the mucosal transcriptome, and luminal microbiota and SCFA concentrations in murine colon. Mice were fed diets enriched with fibers that differed in carbohydrate composition, namely inulin (IN), oligofructose (FOS), arabinoxylan (AX), guar gum (GG), resistant starch (RS) or a control diet (corn starch) for 10 days. Gene expression profiling revealed the regulation of specific, but also overlapping sets of epithelial genes by each fiber, which on a functional level were mainly linked to cell cycle and various metabolic pathways including fatty acid oxidation, tricarboxylic acid cycle, and electron transport chain. In addition, the transcription factor PPAR was predicted to be a prominent upstream regulator of these processes. Microbiota profiles were distinct per dietary fiber, but the fibers IN, FOS, AX and GG induced a common change in microbial groups. All dietary fibers, except resistant starch, increased SCFA concentrations but to a different extent. Multivariate data integration revealed strong correlations between the expression of genes involved in energy metabolism and the relative abundance of bacteria belonging to the group of Clostridium cluster XIVa, that are known butyrate producers. These findings illustrate the potential of multivariate data analysis to unravel simple relationships in complex systems.
Publication Title
Comparison of the effects of five dietary fibers on mucosal transcriptional profiles, and luminal microbiota composition and SCFA concentrations in murine colon.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
Illumina HiSeq 4000
Description
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. However, most siRNAs or shRNAs targeting either CD95 or CD95L induce DICE (Death Induced by CD95/CD95L Elimination), a form of cell death in which a combination of different cell death pathways are activated, that is selective for transformed cells, and that preferentially affects cancer stem cells. We now provide evidence that both CD95 and CD95L are part of a network of genes that contain sequences that when expressed as either siRNAs or shRNAs are toxic to cancer cells. They act through canonical RNAi by targeting the 3''UTRs of critical survival genes. We propose that these embedded toxic sequences are part of a conserved mechanism that regulates cell death, and we predict the existence of endogenous siRNAs, that when produced, induce cell death to regulate genome fidelity. Our data have implications for cancer therapy and the use of RNAi. Overall design: 293T (shL3 site deleted) cells were infected with either pTIP-shScr or pTIP-shL3 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of doxycycline/HeyA8 (shR6 site deleted) cells were infected with either pLKO-shScr or pLKO-shR6 and following puromycin selection large RNAs were analyzed by deep sequencing 50 or 100hrs after addition of selection.
Publication Title
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
A deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) leads to chronic lung disease. However, the molecular mechanisms are not well understood and therapies that can help all patients remain elusive. CF is associated with abnormalities in fatty acids, ceramides and cholesterol, therefore we examined the impact of CFTR deficiency on lipid metabolism and pro-inflammatory signaling in airway epithelium using mass spectrometric, protein array and RNAseq analyses. We observed a striking imbalance in fatty acid and ceramide metabolism, associated with chronic oxidative stress under basal conditions in CF mouse lung and well differentiated bronchial epithelial cell cultures of CFTR knock out pig and CF patients. Cell autonomous features of all three CF models included high ratios of ω-6- to ω-3-polyunsaturated fatty acids and long- to very long- chain ceramide species (LCC/VLCC). The anti-oxidants glutathione (GSH) and deferoxamine partially corrected the lipid profile indicating that oxidative stress may promote the lipid abnormalities. CFTR-targeted modulators reduced the lipid imbalance and apparent oxidative stress, confirming the CFTR dependence of lipid ratios. RNA sequencing and protein array analysis revealed higher expression and shedding of cytokines and growth factors from CF epithelial cells compared to non-CF cells, consistent with sterile inflammation and tissue remodeling under basal conditions. Treatment with antioxidants or CFTR modulators that mimic the approved combination therapies, Orkambi and Trikafta, did not suppress the inflammatory phenotype. These results suggest that anti-inflammatory therapies may provide additional benefit for CF patients taking CFTR modulator drugs. Overall design: Here we report analysis of nine samples, three of Cf patient (BCF000174), homozygous for F508del CFTR, compared to two non-CF in triplicate each (P21, P11, ErasmusMC, Rotterdam, compared pairwise)
Publication Title
CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 4000
Description
We provide evidence that shRNAs and siRNAs derived from CD95 and CD95L preferentially target the 3'' UTRs of survival genes culminating in a very robust mode of cell death we call DISE (Death Induced by Survival gene Elimination) Overall design: 293T cells were infected with either pTIP-shScr or pTIP-shL1 and following puromycin selection RNA was analyzed by deep sequencing 100hrs after addition of doxycycline
Publication Title
Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition of children with a prevalence of 5-10% worldwide. Up to 30% of adults with a history of childhood ADHD maintain symptoms in later life; these adult ADHD patients are severely impaired in social and professional life due to persistence of ADHD core symptoms like impulsivity, attention deficit and hyperactivity as well as frequently observed co-morbidities like alcohol and drug abuse, major depression, bipolar and personality disorders.
Publication Title
A preliminary study on methylphenidate-regulated gene expression in lymphoblastoid cells of ADHD patients.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Our understanding of how mesodermal tissue is formed, has been limited by the absence of specific and reliable markers of early mesoderm commitment. We report that mesoderm commitment from human embryonic stem cells (hESC) is initiated by Epithelial to Mesenchymal transition (EMT) as shown by gene expression profiling and by reciprocal changes in expression of the cell surface proteins, EpCAM/CD326 and NCAM/CD56. Molecular and functional assays reveal that CD326negCD56+ cells, generated from hESC in the presence of activin A, BMP4, VEGF and FGF2, represent a novel, multi-potent mesoderm-committed progenitor population. CD326negCD56+ progenitors are unique in their ability to generate all mesodermal lineages including hematopoietic, endothelial, mesenchymal (bone, cartilage, fat, fibroblast), smooth muscle and cardiomyocytes, while lacking the pluripotency of hESC. CD326negCD56+ cells are the precursors of previously reported, more lineage-restricted mesodermal progenitors. These findings present a novel approach to study how germ layer specification is regulated, and offer a unique target for tissue engineering.
Publication Title
Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Type II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
Publication Title
The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples