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GSE56369
Homo sapiens
25 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The ecto-enzyme CD38 is a marker of unfavorable prognosis for chronic lymphocytic leukemia (CLL) patients and an indicator of activation and proliferation of leukemic cells. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD, CD38 increases cytoplasmic Ca2+ concentrations, positively influencing proliferation, chemotaxis, adhesion and matrix digestion. Inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, increasing responses to chemotherapy.
Publication Title
The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
High grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target. Overall design: Three biological replicates of normal murine 3T3 fibroblasts expressing either control or NNMT overexpression construct were grown for 48 hours in physiological levels of methionine before RNA was collected and sequenced to identify genes differentially regulated in response to NNMT.
Publication Title
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Activating Transcription Factor 4 (ATF4) is a transcription factor induced by the integrated stress response (ISR). This experiment is a genome-wide profiling of ATF4-dependent RNA expression in human HAP-1 cells. HAP-1 is a near-haploid human cell line that was derived from KBM-7 cells isolated from a patient with Chronic Myelogenous Leukemia. We analyzed WT and ATF4 KO cells. We induced ATF4 expression by mimicking amino acid starvation with the drug histidinol. Overall design: RNA expression profiles were generated for WT and ATF4 KO HAP1 cells. ATF4 genes were mutated using Cas9 genome editing technology. Amino acid starvation was mimicked by treating WT and ATF4 KO cells with 2 mM histidinol for 24 hours, which increases ATF4 expression.
Publication Title
A forward genetic screen reveals novel independent regulators of ULBP1, an activating ligand for natural killer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Trypanosoma cruzi is an obligate intracellular protozoan parasite that causes human Chagas disease, a leading cause of heart failure in Latin America. Using Affymetrix oligonucleotide arrays we screened phenotypically diverse human cells (foreskin fibroblasts, microvascular endothelial cells and vascular smooth muscle cells) for a common transcriptional response signature to T. cruzi. A common feature was a prominent type I interferon response, indicative of a secondary response to secreted cytokines. Using transwell plates to distinguish cytokine-dependent and -independent gene expression profiles in T. cruzi-infected cells, a core cytokine-independent response was identified in fibroblasts and endothelial cells that featured metabolic and signaling pathways involved in cell proliferation, amino acid catabolism and response to wounding. Significant downregulation of genes involved in mitotic cell cycle and cell division predicted that T. cruzi infection impedes cell cycle progression in the host cell.
Publication Title
Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The intracellular pathogen Trypanosoma cruzi secretes an activity that blocks TGF--dependent induction of connective tissue growth factor (CTGF/CCN2). Here, we address the mechanistic basis for T. cruzi-mediated interference of
Publication Title
A soluble factor from Trypanosoma cruzi inhibits transforming growth factor-ß-induced MAP kinase activation and gene expression in dermal fibroblasts.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Before and after anaerobic Fe(II) shocked WT and ?bqsR of late stationary phase P. aeruginosa PA14 strains Associated publication: Kreamer NN, Costa F, Newman DK. 2015. The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance. mBio 6(1):e02549-14. doi:10.1128/mBio.02549-14. Overall design: Expression profiles of rRNA-depleted total RNA from WT and ?bqsR Fe(II)-shocked (before and after 30 min incubation with 200 µM ferrous ammonium sulfate ) cultures grown anaerobically to deep stationary phase (A500 = 0.8) in Fe-limited (1 µM ferrous ammonium sulfate) MOPS minimal medium containing succinate as the carbon source, in triplicate
Publication Title
The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mice without macroH2A histone variants.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
MacroH2As core histone variants have a unique structure that includes C-terminal nonhistone domain. MacroH2As are highly conserved in vertebrates, and are thought to regulate gene expression. However the nature of genes regulated by macroH2As and the biological significance of macroH2As for the organism remain unclear. Here we examine macroH2A function in vivo by knocking out both macroH2A1 and macroH2A2 in the mouse.
Publication Title
Mice without macroH2A histone variants.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
MacroH2As core histone variants have a unique structure that includes C-terminal nonhistone domain. MacroH2As are highly conserved in vertebrates, and are thought to regulate gene expression. However the nature of genes regulated by macroH2As and the biological significance of macroH2As for the organism remain unclear. Here we examine macroH2A function in vivo by knocking out both macroH2A1 and macroH2A2 in the mouse.
Publication Title
Mice without macroH2A histone variants.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Follicular lymphoma (FL) is an indolent lymphoma associated with follicular center B cells, and typically contains the Bcl-2 chromosomal translocation t(14;18), which leads to overexpression of the anti-apoptotic intracellular protein Bcl-2. FLs are sensitive to chemotherapy; however, patient relapses occur and response duration becomes progressively shorter, with the majority of patients eventually dying from the disease. Enzastaurin (LY317615), an acyclic bisindolylmaleimide, was initially developed as an ATP-competitive selective inhibitor of PKC. We found, in agreement with recent reports, that enzastaurin inhibits cell proliferation and induces apoptosis. These results are consistent with decreased phosphorylation of the Akt pathway and its downstream targets. To provide new insights into the anti-tumor action of enzastaurin on non-Hodgkin lymphoma, we investigated its effects on gene expression profiles of the B cell lymphoma RL cell line by oligonucleotide microarray analysis. We identified a set of 41 differentially expressed genes, mainly involved in cellular adhesion, apoptosis, inflammation, and immune and defense responses. These observations provide new insights into the mechanisms involved in the induction of apoptosis by enzastaurin in B cell lymphoma cell lines, and identify possible pathways that may contribute to the induction of apoptosis.
Publication Title
Genomic profiling of enzastaurin-treated B cell lymphoma RL cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples