We are investigating the transcriptional response of yeast to treatment with enediynes or gamma radiation, which generate different extents of double or single strand breaks in DNA.
The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA.
No sample metadata fields
View SamplesIdiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF- and IFN- reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF- and IFN--stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-B and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF- and IFN- to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant.
Increased cell surface Fas expression is necessary and sufficient to sensitize lung fibroblasts to Fas ligation-induced apoptosis: implications for fibroblast accumulation in idiopathic pulmonary fibrosis.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesRationale: The fibrosing idiopathic interstitial pneumonias (IIPs) are classified based on clinical, radiographic, and pathologic criteria. The separation into phenotypic subgroups is useful in predicting outcome and therapeutic strategy; however a large degree of ambiguity remains. Gene expression profiling may contribute to traditional criteria in IIPs by characterizing the dynamic biology that more accurately distinguishes subtypes of these diseases or their prognoses.
Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesExhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.
Specimen part, Subject
View SamplesPpp2r1afl/fl mouse bone marrow pre-B cells were transduced with an BCR-ABL1 vector. The BCR-ABL1 transduced Ppp2r1afl/fl pre-B cells were then transduced with an empty vector (EV), or a Cre vector for Cre-mediated PP2A deletion. Effect of PP2A deletion in the BCR-ABL1 pre-B cells were studied by Affymetrix GeneChip Mouse Genome ST1.0 Array
B-Cell-Specific Diversion of Glucose Carbon Utilization Reveals a Unique Vulnerability in B Cell Malignancies.
Specimen part
View SamplesTrypanosoma 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.
Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling.
No sample metadata fields
View SamplesThe 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
A soluble factor from Trypanosoma cruzi inhibits transforming growth factor-ß-induced MAP kinase activation and gene expression in dermal fibroblasts.
Specimen part
View SamplesBefore 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
The ferrous iron-responsive BqsRS two-component system activates genes that promote cationic stress tolerance.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mice without macroH2A histone variants.
Sex, Specimen part
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