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GSE7007
Homo sapiens
39 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Publication Title
Mesenchymal stem cell features of Ewing tumors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
OBJECTIVE: To determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern. METHODS: Macrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1-43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte-macrophage colony-stimulating factor. Cells were stimulated for 24 hours with interferon-gamma (IFNgamma; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real-time quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Microarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN-regulated, and their relative expression indicated a reverse IFN signature in AS patient macrophages, where IFNgamma-up-regulated genes were underexpressed and down-regulated genes were overexpressed. Treatment of macrophages with exogenous IFNgamma normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFNgamma gene was approximately 2-fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls. CONCLUSIONS: Our findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking reverse IFN signature. Together with poor expression and responsiveness of the IFNgamma gene, these results suggest that there may be a relative defect in IFNgamma gene regulation, with autocrine consequences and implications for disease pathogenesis.
Publication Title
Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon-gamma dysregulation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
Ion Torrent S5
Description
Systemic juvenile idiopathic arthritis (SJIA) is a chronic childhood arthropathy with features of autoinflammation. Early inflammatory SJIA is associated with expansion and activation of neutrophils with a sepsis-like phenotype, but neutrophil phenotypes present in longstanding and clinically inactive disease (CID) are unknown. The objective of this study was to examine activated neutrophil subsets, S100 alarmin release, and gene expression signatures in children with a spectrum of SJIA disease activity. Methods: Highly-purified neutrophils were isolated using a two-step procedure of density-gradient centrifugation followed by magnetic-bead based negative selection prior to flow cytometry or cell culture to quantify S100 protein release. Whole transcriptome gene expression profiles were compared in neutrophils from children with both active SJIA and CID. Results: Patients with SJIA and active systemic features demonstrated a higher number of CD16+CD62Llo neutrophil population compared to controls. This neutrophil subset was not seen in patients with CID or patients with active arthritis not exhibiting systemic features. Using imaging flow cytometry, CD16+CD62Llo neutrophils from patients with active SJIA and features of macrophage activation syndrome (MAS) had increased nuclear hypersegmentation compared to CD16+CD62L+ neutrophils. Serum levels of S100A8/A9 and S100A12 were strongly correlated with peripheral blood neutrophil counts. Neutrophils from active SJIA patients did not show enhanced resting S100 protein release; however, regardless of disease activity, neutrophils from SJIA patients did show enhanced S100A8/A9 release upon PMA stimulation compared to control neutrophils. Furthermore, whole transcriptome analysis of highly purified neutrophils from children with active SJIA identified 214 differentially expressed genes compared to neutrophils from healthy controls. The most significantly upregulated gene pathway was Immune System Process, including AIM2, IL18RAP, and NLRC4. Interestingly, this gene set showed intermediate levels of expression in neutrophils from patients with long-standing CID yet persistent serum IL-18 elevation. Indeed, all patient samples regardless of disease activity demonstrated elevated inflammatory gene expression, including inflammasome components and S100A8. Conclusion: We identify features of neutrophil activation in SJIA patients with active disease and CID, including a proinflammatory gene expression signature, reflecting persistent innate immune activation. Taken together, these studies expand understanding of neutrophil function in chronic autoinflammatory disorders such as SJIA. Overall design: Highly purified neutrophils isolated from patients with SJIA and healthy controls
Publication Title
Neutrophils From Children With Systemic Juvenile Idiopathic Arthritis Exhibit Persistent Proinflammatory Activation Despite Long-Standing Clinically Inactive Disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
We sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.
Publication Title
Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Polycomb-group proteins form multimeric protein complexes involved in transcriptional silencing. The Polycomb Repressive complex 2 (PRC2) contains the Suppressor of Zeste-12 protein (Suz12) and the histone methyltransferase Enhancer of Zeste protein-2 (Ezh2). This complex, catalyzing the di- and tri-methylation of histone H3 lysine 27, is essential for embryonic development and stem cell renewal. However, the role of Polycomb-group protein complexes in the control of the intestinal epithelial cell (IEC) phenotype is not known. We investigated the impact of Suz 12 depletion on gene expression in IEC-6 cells.
Publication Title
The histone H3K27 methylation mark regulates intestinal epithelial cell density-dependent proliferation and the inflammatory response.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 130 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.
Publication Title
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjgrens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Publication Title
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We generated gene expression profiles of N2 (wild type) and strain FAS43 (Histone H3.3 null worms containing knockout alleles of all genes with homology to human histone H3.3: his-69, his-70, his-71, his-72, his-74) at embryonic and first larval instar stages. Overall design: RNA was isolated from N2 and H3.3 null mixed-stage embryos and L1 larvae grown at 20°C using Trizol, in duplicates for all samples. RNA-seq libraries were prepared using the Illumina TruSeq protocol.
Publication Title
Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response in <i>Caenorhabditis elegans</i>.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Publication Title
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Sample Metadata Fields
Specimen part
View Samples