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GSE12236
Homo sapiens
40 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events with the GeneChip Human Exon 1.0 ST Array from Affymetrix in lung adenocarcinoma. We found that ~13.3% of the 17800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the overexpression of a novel variant of P16. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
Publication Title
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
Publication Title
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
shRNA-mediated ablation of the RING-finger protein TRIM52 from multiple glioblastoma cell lines reduces proliferation and tumorigenesis. To identify gene signatures underlying this phenomenon, transcritional profile of TRIM52 knockdown cells was compared to control cells. Upon TRIM52 ablation, we find 278 differentially regulated genes. Gene ontology analysis reveals that many of the upregulated genes are associated with glycolysis and biosynthetic processes. Overall design: U87MG glioblastoma cells were stably transduced with doxycycline-inducible shRNA constructs targeting TRIM52 (two different shRNAs) or controls (two different non-targeting shRNAs). Knockdown was induced for five days using 2µg/ml doxycycline. shRNA expressing cells were sorted based on shRNA-coupled GFP expression via flow cytometry. mRNA sequening was performed in duplicate per shRNA cell line.
Publication Title
Human tripartite motif protein 52 is required for cell context-dependent proliferation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Steroid hormones regulate essential physiological processes and inadequate levels are associated with various pathological conditions. In testosterone-producing Leydig cells, steroidogenesis is strongly stimulated by LH via its receptor leading to increased cAMP production and expression of the steroidogenic acute regulatory (STAR) protein, which is essential for the initiation of steroidogenesis. Leydig cell steroidogenesis then passively decreases following the rapid degradation of cAMP into AMP by phosphodiesterases. In this study, we show that AMP-activated protein kinase (AMPK) is activated following cAMP breakdown in MA-10 and MLTC-1 Leydig cells. Activated AMPK then actively inhibits cAMP-induced steroidogenesis by repressing the expression of key regulators of steroidogenesis including Star and Nr4a1. Similar results were obtained in Y-1 adrenal cells and in the constitutive steroidogenic cell line R2C. Our data identify AMPK as an active repressor of steroid hormone biosynthesis in steroidogenic cells that is essential to preserve cellular energy and prevent excess steroid production.
Publication Title
A cell-autonomous molecular cascade initiated by AMP-activated protein kinase represses steroidogenesis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- NextSeq 550
Description
We obtained single-cell RNA-sequencing (scRNA-seq) profiles of CD14+ monocytes isolated from human peripheral blood at 0, 3 and 6 days after M-CSF stimulation (to differentiate the cells into macrophages) across multiple donors. Integration of single-cell RNA sequencing (scRNA-seq) data from multiple experiments, laboratories, and technologies can uncover biological insights, but current methods for scRNA-seq data integration are limited by a requirement for datasets to derive from functionally similar cells. We use a novel algorithm, Scanorama, to identify and merge the shared cell types among all pairs of datasets and to accurately integrate heterogeneous scRNA-seq datasets. Scanorama is sensitive to subtle temporal changes within the same cell lineage, successfully integrating functionally similar cells across time series data of CD14+ monocytes at different stages of differentiation into macrophages. Scanorama is not only able to differentiate between completely disparate cell types but is also sensitive to subtler transcriptional changes within a cell type due to processes like stimulation. Overall design: scRNA-seq of human CD14+ monocytes at 0, 3, and 6 days after M-CSF stimulation in multiple donors
Publication Title
Efficient integration of heterogeneous single-cell transcriptomes using Scanorama.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs. immature neurons. We used immature (d0) and mature (d6) LUHMES cells (dopaminergic human neurons) to provide initial answers to these questions. Transcriptome profiling and characterization of energy metabolism suggested a switch from predominantly glycolytic energy generation to a more pronounced contribution of the tricarboxylic acid cycle (TCA) during neuronal maturation. Therefore, we used pulsed stable isotope-resolved metabolomics (pSIRM) to determine intracellular metabolite pool sizes (concentrations), and isotopically non-stationary 13C-metabolic flux analysis (INST 13C MFA) to calculate metabolic fluxes. We found that d0 cells mainly use glutamine to fuel the TCA. Furthermore, they rely on extracellular pyruvate to allow continuous growth. This metabolic situation does not allow for mitochondrial or glycolytic spare capacity, i.e. the ability to adapt energy generation to altered needs. Accordingly, neuronal precursor cells displayed a higher sensitivity to several mitochondrial toxicants than mature neurons differentiated from them. In summary, this study shows that precursor cells lose their glutamine dependency during differentiation while they gain flexibility of energy generation and thereby increase their resistance to low concentrations of mitochondrial toxicants.
Publication Title
Stage-specific metabolic features of differentiating neurons: Implications for toxicant sensitivity.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Disruption of N-linked glycosylation has a broad impact on proper glycosylation of nascent glycoproteins in the endoplasmic reticulum, which affect multiple signalling pathways( by changing the stability of membrane proteins or the signalling ability of membrane receptors) and may be responsible of the fibrotic stage associated to CDG type-I.
Publication Title
Fibrotic response in fibroblasts from congenital disorders of glycosylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 16 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant and wild type Drosophila larvae
Publication Title
Genome-wide expression analysis identifies a modulator of ionizing radiation-induced p53-independent apoptosis in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) is a transcription factor recently identified in somatic cells of the male gonad. In other tissues, MEF2 is an essential regulator of organogenesis and cell differentiation. So far in the testis, MEF2 was found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MA-10 Leydig cells depleted in MEF2 and results were analyzed using the Partek and IPA softwares. Several genes were differentially expressed in MEF2-depleted Leydig cells and 15 were validated by qPCR. A large number of these genes are known to be involved in fertility, gonad morphology and steroidogenesis and include Pde8a, Por, Ahr, Bmal1, Cyp1a1, Cyp1b1, Map2k1, Tsc22d3, Nr0b2, Smad4, and Star, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2 binding sites within the first 2 kb upstream the transcription start site of the Por, Bmal1, and Nr0b2 promoters, which suggests a direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, siRNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1 and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction.
Publication Title
Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Exploring the expression profile of ovarian clear cell carcinoma cancer cell subpopulations- derived tumors grown within a murine and a human cellular tissues.
Publication Title
Niche-dependent gene expression profile of intratumoral heterogeneous ovarian cancer stem cell populations.
Sample Metadata Fields
Specimen part
View Samples