Mutations in the RUNX1 gene (RUNX1mut) have been established in myelodysplasia (MDS), de novo and secondary acute myeloid leukaemia (AML), and are in general associated with an unfavourable clinical outcome. Familial RUNX1 mutations are associated with familial thrombocytopenia and these patients have a predisposition to AML development. However, a number of studies have been performed so far in mice which might be distinct from the human hematopoietic system. Therefore we studied the cellular phenotypes, the RUNX1 binding pattern and expression profile induced by RUNX1mut in cord blood (CB) CD34+ cells and induced pluripotent stem cell (iPSC) and compared these findings to primary RUNX1mut AML's. Overall design: A total of nine samples were subject to RNA-Seq including RUNX1mut-transduced cord blood CD34 cells and time-course iPSCs.
RUNX1 mutations enhance self-renewal and block granulocytic differentiation in human in vitro models and primary AMLs.
Specimen part, Subject
View SamplesWe have combined large-scale mRNA expression and gene mapping methods to identify genes and loci that control hematopoietic stem cell (HSC) functioning. mRNA expression levels were measured in purified HSC isolated from a panel of densely genotyped recombinant inbred mouse strains. Quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts were mapped. Comparison of the physical transcript position with the location of the controlling QTL identified polymorphic cis-acting stem cell genes. In addition, multiple trans-acting control loci were highlighted that modify expression of large numbers of genes. These groups of co-regulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of strong candidate genes involved with HSC turnover. We compared expression QTLs in HSC and brain from the same animals, and document both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of co-regulated transcripts.
Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.
No sample metadata fields
View SamplesIn order to identify relevant, molecularly defined subgroups in Multiple Myeloma (MM), gene expression profiling (GEP) was performed on purified CD138+ plasma cells of 320 newly diagnosed myeloma patients included in the Dutch-Belgian/German HOVON-65/ GMMG-HD4 trial using Affymetrix GeneChip U133 plus 2.0 arrays. Hierarchical clustering identified 10 distinct subgroups. Using this dataset as training data, a prognostic signature was built. The dataset consists of 282 CEL files previously used in the hierarchical clustering study of Broyl et al (Blood, 116(14):2543-53, 2010) outlined above. To this set 8 CEL-files/gene expression profiles were added. Using this set of 290 CEL-files, a prognostic signature of 92 genes (EMC-92-genesignature) was generated by supervised principal components analysis combined with simulated annealing (Kuiper et al.).
Gene expression profiling for molecular classification of multiple myeloma in newly diagnosed patients.
Specimen part
View SamplesStaphylococcus aureus enterotoxins cause debilitating systemic inflammatory responses, but how they spread systemically and trigger cascading inflammation is unclear. Here, we showed in mice that after inhalation, Staphylococcus aureus enterotoxin A rapidly entered the bloodstream and induced T cells to orchestrate systemic recruitment of inflammatory monocytes and neutrophils. To study the mechanism used by specific T cells that mediate this process, a systems approach revealed inducible and non-inducible pathways as potential targets. It was found that TNF induced neutrophil entry into the peripheral blood, while CD28 signaling, but not TNF, was needed for chemotaxis of inflammatory monocytes into blood and lymphoid tissue. However, both pathways triggered local recruitment of neutrophils into lymph nodes. Thus, our findings revealed a dual mechanism of monocyte and neutrophil recruitment by T cells relying on overlapping and non-overlapping roles for the non-inducible costimulatory receptor CD28 and the inflammatory cytokine TNF. During sepsis, there might be clinical value in inhibiting CD28 signaling to decrease T cell-mediated inflammation and recruitment of innate cells while retaining bioactive TNF to foster neutrophil circulation. Overall design: The purpose of this analysis was to determine changes in gene expression in SEA-specific Vß3+ T cells and bystander T Vß14+ cells 40 min after SEA or vehicle inhalation.The samples were collected from three independent experiments with total n=3 per group. Three groups of samples were prepared: vehicle Vß3+ T cells, SEA Vß3+ T cells, and SEA Vß14+ T cells.
TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Yin Yang 1 extends the Myc-related transcription factors network in embryonic stem cells.
Specimen part
View SamplesWe have determined the global gene expression upon loss of function of the Yy1 transcription factor in mouse embryonic stem cells
Yin Yang 1 extends the Myc-related transcription factors network in embryonic stem cells.
Specimen part
View SamplesAffymetrix gene expression data of 21 high-grade osteosarcomas located in the extremities.This gene expression profiling was performed in order to evaluate the expression of candidate prognostic and therapeutic targets in high-grade osteosarcoma.
Targeting CDKs with Roscovitine Increases Sensitivity to DNA Damaging Drugs of Human Osteosarcoma Cells.
Age, Specimen part
View SamplesAndrogens are required for the development of normal prostate, and they are also linked to the development of prostate cancer.
Proteomic interrogation of androgen action in prostate cancer cells reveals roles of aminoacyl tRNA synthetases.
Specimen part, Cell line
View SamplesMicroarray was used to study global gene expression of a cell culture model based on SV40-immortalized human corneal epithelial (iHCE) cells. The gene expression profile of the cell line was compared to the normal human corneal epithelium. Affymetrix HG-U133A GeneChips were used for microarray experiments and results were validated by performing RT-qPCR for selected genes. iHCE was found to over- and under-express 22 % and 14 % of the annotated genes, respectively. The results of this study suggest that differences between iHCE cells and normal corneal epithelium are substantial and therefore the use of these cells in corneal research should be considered with caution.
Gene expression analysis in SV-40 immortalized human corneal epithelial cells cultured with an air-liquid interface.
Cell line
View SamplesPurpose: Utilized Next-generation sequencing (NGS) to profile transcriptional differences between two populations, carriers (CC) of rs10846744 SNP associated with cardiovascular disease (CVD) and non-carriers (GG) who are disease free. Methods: Total RNA was isolated from three subjects homozygous for the rs10846744 reference (GG) allele and three subjects homozygous for the rs10846744 risk (CC) allele and then subjected to full transcriptome sequencing using the Perkin Elmer next gen sequencing platform (Perkin Elmer, Branford, CT). Bioinformatics was performed using Perkin Elmer GeneSifter software program. The data was adjusted by selecting total map reads, quality reads >20, log transformation, and using Benjamini Hochberg to correct for multiple testing. RNA targets of interest were validated by qRT–PCR using TaqMan assays and western blotting using standard methodologies. Results: Using Perkin Elmer''s Genesifter Analysis Edition Software, we mapped about 100 million sequence reads per sample to the human genome (build 37.2), normalized the raw read count by total mapped million reads and identified 937 upregulated and 587 downregulated transcripts in the EBV (Epstein Barr Virus)-transformed B lymphocyte cells isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele with BWA workflow. RNA-seq data confirmed differential expression of LAG3 and this was validated with qRT–PCR. Conclusions: Our study represents the first detailed analysis of differential LAG3 expression, contributing to CVD, with biologic replicates, generated by RNA-seq technology. Overall design: mRNA transcriptional profiles from EBV (Epstein Barr Virus)-transformed B lymphocyte cells, isolated from 3 carriers of the risk (CC) allele and 3 non-carriers of the (GG) reference allele, were generated by deep sequencing, in triplicate, using Illumina platform technology.
Lymphocyte activation gene 3 and coronary artery disease.
Specimen part, Subject
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