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GSE69269
Homo sapiens
13 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR// were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.
Publication Title
Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to better understand the factors that regulate B cell differentiation upon exposure to antigen, we compares global gene expression profiles from naive B cells with antigen-specific plasma, germinal center, and memory B cells after immunization with the T-dependent antigen, NP-CGG. The memory B cell-enriched transcripts were then compared with memory T cell-enriched and hematopoietic stem cell-enriched transcripts in order to generate a transcriptional profile of self-renewal within the hematopoietic system.
Publication Title
Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Affymetric arrays were performed on thyroid samples collected from GEMMs: normal thyroid, TPO-Cre/LSL-Braf (PTC), TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (ATC) and TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (recurrent tumors)
Publication Title
Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 75 Downloadable Samples
NextSeq 500, Illumina HiSeq 2500
Description
IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression was associated with reduced survival in CD4+ T cells undergoing lymphopenia-induced proliferation (LIP). We propose a model in which T cells undergoing LIP upregulate STAT1 protein, "switching on" an alternate IL-7-dependent program. This mechanism could be a physiological process to regulate the expansion and size of the CD4+ T cell pool. During HIV infection, the virus could exploit this pathway, leading to the homeostatic dysregulation of the T cell pools observed in these patients. Overall design: Sorted naive CD4 T and CD8 T cells from WT or STAT1 transgenic mice were stimulated for 90 minutes with IL-7 or IFNg. Additonally CD4 T cells from WT or STAT1 trangenic or IL7Ra449F transgenic mice were stimulated for overnight with IL-7 or IFNg or IFNa4. Up to four biological replicates tested for each condition.
Publication Title
IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using global gene expression and proteomic analyses, we identified a molecular signature in human embryonic and induced pluripotent stem cells that suggested a central regulatory role for RNA splicing in self-renewal. Through genetic and biochemical approaches, we established reciprocal functional links between the master regulatory factor OCT4 and SFRS2, a member of the serine/arginine-rich family of splicing factors. SFRS2 regulates expression of two isoforms of the methyl-CpG-binding protein MBD2 that play opposing roles in human ESC and during the reprogramming of fibroblasts. Both the MBD2a isoform expressed in fibroblasts and the MBD2c isoform found in pluripotent cells bind OCT4 and NANOG promoters in human ESC, but only MBD2a interacts with NuRD chromatin remodeling factors. Members of the miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and the somatic specific MBD2a isoform. These data are consistent with a model in which OCT4, SFRS2, and MBD2 participate in a positive feedback loop to regulate proteome diversity in support of self-renewal in pluripotent cells.
Publication Title
Alternative splicing of MBD2 supports self-renewal in human pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Fundamental research and drug development for personalized medicine necessitates cell cultures from defined genetic backgrounds. However, providing sufficient numbers of authentic cells from individuals poses a challenge. Here, we present a new strategy for rapid cell expansion that overcomes current limitations. Using a small gene library, we expanded primary cells from different tissues, donors and species. Cell type specific regimens that allow the reproducible creation of cell lines were identified. In depth characterization of a series of endothelial and hepatocytic cell lines confirmed phenotypic stability and functionality. Applying this technology enables rapid, efficient and reliable production of unlimited numbers of personalized cells. As such, these cell systems support mechanistic studies, epidemiological research and tailored drug development.
Publication Title
Expansion of functional personalized cells with specific transgene combinations.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine complementary analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions that demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
HepG2 and THP-1 cells, the latter differentiated by phorbol 12-myristate 13-acetate (PMA), were co-cultured and characterized for typical liver-specific functions, such as xenobiotic detoxification, lipid and cholesterol metabolism. Furthermore, liver injury-associated pathways, such as inflammation, were studied. In general, the co-cultivation of these cells produced a pro-inflammatory system, as indicated by increased levels of cytokines (IL-8, TGF-α, IL-6, GM-CSF, G-CSF, TGF-β, and hFGF) in the respective supernatant. Increased expression levels of target genes of the aryl hydrocarbon receptor (AHR), e.g., CYP1A1, CYP1A2 and CYP1B1, were detected, accompanied by the increased enzyme activity of CYP1A1. Moreover, transcriptome analyses indicated a significant upregulation of cholesterol biosynthesis, which could be reduced to baseline levels by lovastatin. In contrast, total de novo lipid synthesis was reduced in co-cultured HepG2 cells. Key events of the adverse outcome pathway (AOP) for fibrosis were activated by the co-cultivation, however, no increase in the concentration of extracellular collagen was detected. This indicates, that AOP should be used with care. In summary, the indirect co-culture of HepG2/THP 1 cells results in an increased release of pro-inflammatory cytokines, an activation of the AHR pathway and an increased enzymatic CYP1A activity.
Publication Title
Indirect co-cultivation of HepG2 with differentiated THP-1 cells induces AHR signalling and release of pro-inflammatory cytokines.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Double-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood. Here we show that human Staufen1-containing complexes contain essential elements of the gene silencing apparatus, like Ago1-3 proteins, and we describe a set of miRNAs specifically associated to complexes containing human Staufen1. Among these, miR124 stands out as particularly relevant because it appears enriched in human Staufen1 complexes and is over-expressed upon differentiation of human neuroblastoma cells in vitro. In agreement with these findings, we show that expression of human Staufen1 is essential for proper dendritic arborisation during neuroblastoma cell differentiation, yet it is not necessary for maintenance of the differentiated state, and suggest potential human Staufen1 mRNA targets involved in this process.
Publication Title
Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation.
Sample Metadata Fields
Cell line
View Samples