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GSE5716
Homo sapiens
40 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSI), which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Analysis of gene expression in GSI-responsive and GSI-resistant cell lines treated with Compound E identifies differential resopnses to GSI.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gain-of-function mutations in NOTCH1 are common in T-cell lymphoblastic leukemias making this receptor a promising target for drugs such as gamma-secretase inhibitors, which block a proteolytic cleavage required for NOTCH1 activation. However, the enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by oncogenic NOTCH1. Here we show that NOTCH1 regulates PTEN expression and the activity of the PI3K-AKT signaling pathway in normal and leukemic T cells. Notch signaling and the PI3K-AKT pathway synergize in vivo in a Drosophila model of Notch-induced tumorigenesis, and mutational loss of PTEN is associated with increased glycolysis and resistance to NOTCH1 inhibition in human T-ALL. These findings identify the transcriptional regulation of PTEN and the control of cellular metabolism as key elements of the oncogenic program activated by NOTCH1 and provide the basis for the design of new therapeutic strategies for T-ALL.
Publication Title
Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Sus scrofa
- 14 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Innate immune response is the first line of antiviral defense resulting, in most cases, in pathogen clearance with minimal clinical consequences. Viruses have developed diverse strategies to evade innate immune response and to ensure their survival. Using transmissible gastroenteritis virus (TGEV) as a model, we previously reported that accessory gene 7 counteracts host antiviral response by its association with the catalytic subunit of protein phosphatase 1 (PP1c). A transcriptomic analysis was performed to further investigate the effect of gene 7 absence on the host cell.
Publication Title
Alphacoronavirus protein 7 modulates host innate immune response.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: In the last decade, much attention has been drawn to probiotic bacteria in the context of inflammatory bowel disease (IBD), since the potential of certain strains to attenuate inflammation was demonstrated in several animal experiments and clinical studies. Data in humans elucidating the molecular mechanism of probiotic action are still scarce. To this end, we used an organ culture system of human colon mucosa and investigated the gene expression profiles after treatment with different probiotic bacteria in phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO)) stimulated samples using whole genome microarrays. Moreover, we analyzed changes occurring in the intestinal explants cultured for 8 hours when compared to fresh, directly frozen mucosa, in order to infer the suitability of the system to study an inflammatory stimulus and likely antiinflammatory responses. Results: Culturing intestinal colon fragments during 8 hours elicited differential gene expression in 283 genes, 229 upregulated and 54 downregulated. Upregulated genes were predominantly related to apoptosis, whereas downregulated genes encoded mitochondrial proteins. No specific enrichment of genes related to inflammation or immune response could be detected, confirming the suitability of the system to further study the inmunomodulatory/anti-inflammatory properties of Lactobacillus casei BL23 (BL23), L.plantarum 299v (LP299v) and L.plantarum 299v (A-) (LP299v (A-)), a mutant strain with reduced adhesive properties to enterocytes. Intestinal explants were stimulated with PMA/IO for 3 hours and subsequently incubated with probiotic bacteria for 4 h. ANOVA analysis (p 0,01) revealed 205 differentially expressed genes between Control, PMA/IO (Inflamed), and the 3 bacterial treatments. Most importantly, a number of PMA/IO induced genes related to immune response and immune system process such as IL-2, IFN-, IL17A and pro-inflammatory cytokines CXCL9 and CXCL11 were downregulated by BL23, LP299v and LP299v (A-). The behaviour of the three Lactobacillus strains was quite similar, although their presence induced differential expression of a small number of genes in a strain dependent manner. Conclusion: The human colon organ culture was found to be a suitable model for the study of inflammatory/anti-inflammatory stimuli, and therefore it constitutes a valuable tool to determine the inmunomodulatory effect of probiotic bacteria. The global transcriptional profile evoked by strains BL23, LP299v and LP299v (A-) in artificially inflamed tissue indicated a clear homeostasis restoring effect, including a decrease of the signals produced by activated T cells.
Publication Title
Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We analyzed gene expression in CD4+ cells sorted from naïve or D30 Mycobacterium tuberculosis-infected mice and incubated in vitro in the presence or absence of Schistosoma egg antigen. We found genes associated with Th1 function, T cell signaling, T cell costimulation and T cell activation were downregulated in SEA-treated cells, while expression of Th2 cytokines was below the threshold for detection. Overall design: RNAseq results for 3 replicates for naïve or CD4+ T cells from M.tuberculosis-infected mice treated with or without Schistosoma egg antigen in vitro.
Publication Title
Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
We report the phenotype of human lung ILC2 and ILC3 populations from individuals with tuberculosis (TB) and non-TB cancer controls. We find that ILC2s demonstrate moderate transcriptional differences in TB infection, whereas ILC3s demonstrate large differences. Overall design: ILC2s and ILC3s were purified by FACS from lung biopsies from TB infected lung tissue and peripheral healthy lung tissue from individuals with cancer. Low-input RNA-seq was performed on 1-3 replicates (dependent on cell number) on 5 individuals with TB infection and 2 controls.
Publication Title
Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples