Head and neck cancer is a hetergeneous disease. Based on previoulsy defined molecular subtypes we associated gene expression with response to different compounds. We used microarry gene expression for molecular subtyping
Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer.
No sample metadata fields
View SamplesEmbryonic chicken telencephalon nuclei were isolated for RNAseq to identify transcripts differentially expressed across different brain regions.
Neocortical Association Cell Types in the Forebrain of Birds and Alligators.
Sex, Specimen part
View SamplesCD4+ cells from Foxp3.eGFP mice containing Foxp3- Teff and Foxp3+ Treg cells were treated with anti-CD3/CD28 monoclonal antibodies or soluble OX40L and JAG1 for 3 days to induce TCR-dependent vs TCR-independent Treg proliferation. Untreated fresh CD4+ T-cells used as control. Post treatment T-cell proliferation was confirmed by Cell Trace violet dilution and Foxp3+ (Treg) and Foxp3-(Teff) were sorted. Differential gene expression profiling between Tregs and Teff cells among control, anti-CD3/CD28 and OX40L-JAG1 treated cultured was performed using affymetrix mouse gene 2.0 ST micro array.
OX40L-JAG1-Induced Expansion of Lineage-Stable Regulatory T Cells Involves Noncanonical NF-κB Signaling.
Specimen part, Treatment
View SamplesWe investigated the role of mTORC1 in murine hematopoiesis by conditionally deleting the Raptor gene in murine hematopoietic stem cells. We observed mutliple alterations evoked by Raptor loss in hematopoiesis and profiled gene-expression alterations induced by raptor loss in Flt3-Lin-Sca1+cKit+ hematopoietic stem and progenitor enriched cell populations, 5 weeks post Raptor deletion.
mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis.
Specimen part
View SamplesAberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPAR signaling pathway as a feature of AML expressing CDX2, and observed that PPAR agonists derepress KLF4 and are preferentially toxic to CDX2-positive leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells; provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer; and suggest reactivation of KLF4 expression, through modulation of PPAR signaling, as a new therapeutic modality in a large proportion of AML patients.
CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling.
No sample metadata fields
View SamplesWe used IMR90 ER:RAS cells infected with an empty vector or an shRNA for ARID1B and induced senescence by addition of 4OHT. 6 days later RNA was collected for gene expression analysis. With a functional screen we previously identified ARID1B as a new regulator of cellular senescence. By performing gene expression analysis we confirmed this finding and showed that knockdown of ARID1B prevents the expression of genes induced during senescence.
SWI/SNF regulates a transcriptional program that induces senescence to prevent liver cancer.
Cell line
View SamplesRoom temperature whole blood mRNA stabilization procedures, such as the PAX gene system, are critical for the application of transcriptional analysis to population-based clinical studies. Global transcriptome analysis of whole blood RNA using microarrays has proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA in the blood. This is a particular problem in patients with sickle-cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation . In order to more accurately measure the steady state whole blood transcriptome in sickle-cell patients, we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA samples for genome-wide transcriptome analyses using oligonucleotide arrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle-cell disease patients. This led to an improvement in microarray data quality with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. The differentially modulated genes from the globin depleted samples had a higher correlation coefficient to the 112 genes identified to be significantly altered in our previous study on sickle-cell disease using PBMC preparations. Additionally, the analysis of differences between the whole blood transcriptome and PBMC transcriptome reveals important erythrocyte genes that participate in sickle-cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases and in multicenter clinical trials investigating a wide range of nonhematologic disorders where fractionation of cell types is impracticable.
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease.
Specimen part, Subject
View SamplesWe are investigating the response of human lymphoblastoid cells to low-dose exposure of environmental metals
Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium.
Cell line, Treatment
View SamplesThe ER stress inducing agent Thapsigargin (TG) and/or the cytoprotective agent Salubrinal were applied to lymphoblastoid cell lines. TG induced lytic replication as well as a distinct pattern of gene expression changes. This study was designed to identify host genes mediating lytic replication secondary to ER stress.
Endoplasmic reticulum stress causes EBV lytic replication.
Specimen part, Treatment, Time
View SamplesAdjacent alternative 3’ splice sites, those separated by =18nt, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron''s 3'' end depends upon sequence elements that define the branchpoint, polypyrimidine tract and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched C. elegans samples, we identify hundreds of introns with adjacent alternative 3’ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is mono-directional, with somatic cells preferring to splice at the distal 3'' splice site and germline cells showing a distinct shift towards usage of the adjacent proximal 3'' splice site. Splicing patterns in somatic cells follow consensus rules of 3’ splice site definition, using sites with a short stretch of pyrimidines and an AG dinucleotide. Splicing in germline cells occurs at proximal 3'' splice sites that frequently lack a polypyrimidine tract or, occasionally, the AG dinucleotide. We provide evidence that use of germline-specific proximal 3'' splice sites is conserved across Caenorhabditis species. We propose that divergent mechanisms exist between germline and somatic cells in determining an intron terminus at adjacent alternative 3’ splice sites. Overall design: Examination of alternative splicing changes between germline- and somatic-cell enriched samples as well as nonsense-mediated decay mutants.
Coordinated tissue-specific regulation of adjacent alternative 3' splice sites in C. elegans.
Specimen part, Cell line, Subject
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