Ewing sarcoma family of tumors (ESFT) are aggressive bone and soft tissue tumors of unknown cellular origin. Most ESFT express EWS-FLI1, a chimeric protein which functions as a growth-promoting oncogene in ESFT but is toxic to most normal cells. A major difficulty in understanding EWS-FLI1 function has been the lack of an adequate model in which to study EWS-FLI1-induced transformation. Although the cell of origin of ESFT remains elusive, both mesenchymal (MSC) and neural crest (NCSC) have been implicated. We recently developed the tools to generate NCSC from human embryonic stem cells (hNCSC). In the current study we used this model to test the hypothesis that neural crest-derived stem cells are the cells of origin of ESFT and to evaluate the consequences of EWS-FLI1 expression on human neural crest biology.
Modeling initiation of Ewing sarcoma in human neural crest cells.
Specimen part
View SamplesCentrosome defects are a common feature of many cancers. Surprisingly, flies can proceed through the majority of development without centrosomes or with amplified centrosomes in most of their cells. It is unclear whether this is because centrosome defects do not cause many problems in Drosophila cells, or because they can adapt to cope with any problems that arise. Indeed, centrosome loss and centrosome amplification predispose fly brain cells to form tumours. Here we assess how centrosome loss or centrosome amplification perturbs cell physiology by profiling the global transcriptome of Drosophila larval brains and imaginal discs that either lack centrosomes or have too many centrosomes.
Centrosome loss or amplification does not dramatically perturb global gene expression in Drosophila.
Specimen part
View SamplesTranscript profiling analysis of csn3-1, csn4-1 and csn5 (csn5a-2 csn5b) light grown and dark grown mutant seedlings compared to light grown and dark grown wild type using Arabidopsis ATH1 GeneChip array
The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability.
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View SamplesTo elucidate the gene expression footprint of antigenically challenged T-cells which had been treated with anti-LFA-1, CTLA4Ig, anti-CD40-ligand antibodies, we performed microarray gene expression analysis comparing the expression profile of costimulatory blockade treated and untreated responder T-cells.
Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells.
Specimen part
View SamplesRNA seq analysis for pathwayidentification to identify Overall design: RNA Seq analysis of apoptotic resistant and WT neutrophils isolated from bone marrow and peritoneum after thiglycollate induced inflammation
Programmed cell removal by calreticulin in tissue homeostasis and cancer.
Specimen part, Cell line, Subject
View SamplesHuman engeneered skin carrying GFP positive melanoma cells was transplanted in immunocompromised rats.
low neurotrophin receptor CD271 regulates phenotype switching in melanoma.
Specimen part, Time
View SamplesAffymetrix exon array data were generated from total RNA that was isolated from localized Ewing sarcoma biopsy specimens. Expression of transcript summarized data was compared to data generated from normal stem cells and normal adult tissues.
Overexpression of HOX genes is prevalent in Ewing sarcoma and is associated with altered epigenetic regulation of developmental transcription programs.
Specimen part
View SamplesChanges in Treg function are difficult to quantify due to the lack of Treg-exclusive markers in humans and the complexity of functional experiments. We sorted naive and memory human Tregs and conventional T cells, and identified genes that identify human Tregs regardless of their state of activation. We developed this Treg signature using Affymetrix human genome U133A 2.0 microarrays.
A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes.
Treatment, Subject
View SamplesGlucosamine proved to be a potent, broad-spectrum inhibitor of IL-1beta. Of the 2,813 genes whose transcription was altered by IL-1beta stimulation (p<0.0001), glucosamine significantly blocked the response in 2,055 (~73%). Glucosamine fully protected the chondrocytes from IL-1-induced expression of inflammatory cytokines, chemokines and growth factors as well as proteins involved in PGE2 and NO synthesis. It also blocked the IL-1-induced expression of matrix specific proteases such as MMPs -3,-9,-10,-12 and ADAMTS-1.
Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta.
Age
View SamplesWe have shown that activin promoted skin tumorigenesis in mice induced by the human papilloma virus 8 oncogenes. Activin attracted blood monocytes to the skin as revealed by depletion of CCR2-positive monocytes. To determine if activin also altered the gene expression profile of these cells, we performed RNA-Sequencing of macrophages FACS-sorted from the pre-cancerous ear skin. We have found that activin induces a pro-migratiory, pro-angiogenic and pro-tumorigenic genes in skin macrophages in vivo. This largely contributes to the pro-tumorigenic function of activin, since macrophage depletion delayed spontaneous tumorigenesis in HPV8-transgenic mice by reducing keratinocyte proliferation and angiogenesis. Overall design: F4/80+CD11b+CD45+ cells were FACS-sorted from the pre-cancerous ear skin of wt/wt, HPV8/wt, wt/Act and HPV8/Act mice and their expression profile was analysed by RNA-Sequencing. Experiment was performed in triplicates, for each replicate ear skin of 3-6 mice of corresponding genotype was pooled.
Activin promotes skin carcinogenesis by attraction and reprogramming of macrophages.
Specimen part, Cell line, Subject
View Samples