Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting, but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy.
Extracellular matrix protein CCN1 limits oncolytic efficacy in glioma.
Cell line
View SamplesWe present a detailed single cell time course of the macrophage response to Salmonella infection. By combining phenotypic fluorescent labels with single cell expression analysis we are able to identify gene modules associated with bacterial exposure and bacterial infection. We also identify other genetic clusters that are expressed heterogenously, ananlyzing both their regulation and their impact on infection Overall design: Analysis of 192 single cells across 4 time points after Salmonella exposure (MOI 1:1) with one of three different fluorescent labels indicating whether a given cell contained no intracellular bacteria (non-fluorescent), contained dead intracellular bacteria (only pHrodo positive), or contained live intracellular bacteria (pHrodo and GFP positive)
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.
No sample metadata fields
View SamplesWe present a detailed single cell analysis of the macrophage response to LPS from Salmonella enterica. By combining single cell transcriptional analysis, fluorescently labeled, LPS-coated beads, and cytometry we are able to distinguish the responses of macrophages that have internalized LPS-coated beads and those that have not. Overall design: Analysis of 96 single macrophages that were either: left untreated, were exposed to but did not internalize uncoated beads, were exposed to and internalized uncoated beads, were exposed to but did not internalize LPS-coated beads, or were exposed to and did internalize LPS-coated beads.
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.
No sample metadata fields
View SamplesA time course of the macrophage response to Salmonella exposure analyzing the effects of input cell number as a control for single cell studies Overall design: Mouse macrophages were exposed to Salmonella enterica for different lengths of time. Libraries were constructed using either approximately 500,00 macrophages lysed directly on a tissue culture dish (bulk) or using only 150 cells isolated using FACS (sorted). All libraries were constructed in duplicate (bulk) or triplicate (sorted). All replicates are biological replicates
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses.
No sample metadata fields
View SamplesBoron is an essential micronutrient for plants and is taken up in the form of boric acid (BA). Despite this, a high BA concentration is toxic for the plants, inhibiting root growth and is thus a significant problem in semi-arid areas in the world. In this work, we report the molecular basis for the inhibition of root growth caused by boron. We used microarrays to detail the global gene expression underlying boron toxicity in roots.
A molecular framework for the inhibition of Arabidopsis root growth in response to boron toxicity.
Specimen part, Treatment
View SamplesIn tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing the surrounding vasculature network. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines responded strikingly different to hypoxia. We demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response. Overall design: 16 paired-end samples in total: 4 different cell lines sequenced in duplicate across 2 conditions each.
Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.
Specimen part, Treatment, Subject
View SamplesMalignant mesothelioma (MM) is an asbestos-related malignancy and largely unresponsive to conventional chemotherapy or radiotherapy. Novel, more effective therapeutic strategies are needed for this fatal disease. We performed microarray analysis of MM using Affymetrix Human U133 Plus 2.0 array. Aberrant expression of the genes participating in semaphorin signaling were detected in malignant mesothelioma cells. All MM cells downregulated the expression of more than one gene for SEMA3B, 3F, and 3G when compared with Met5a, a normal pleura-derived cell line. In 12 of 14 epithelioid MM cells, the expression level of SEMA3A was lower than that in Met5a. An augmented expression of VEGFA was detected in half of the MM cells. The expression ratio of VEGFA/SEMA3A was significantly higher in the epithelioid MMs than in Met5a and the non-epithelioid MMs. Next, gene expression profiling for the polycomb and trithorax group genes revealed that expression of BAP1, the catalytic subunit of the polycomb repressive deubiquitinase complex, and many trithorax group genes was downregulated in MMs compared with the expression of the same genes in Met5a cells. Perturbation of the polycombtrithorax balance plays a significant role in the pathogenesis of malignant mesothelioma.
Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.
Sex, Age, Specimen part, Cell line
View SamplesGametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells. Overall design: RNA-seq and ChIP-seq analyses using wild-type and Scml2-KO spermatogenic cells
Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis transition in the male germline.
No sample metadata fields
View SamplesGene expression data from mouse organs after Advax injection
Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.
Sex, Specimen part
View SamplesTranscriptional profiling of oral keratinocytes was utilized to define the biological role of P. gingivalis SerB.
Role of Porphyromonas gingivalis SerB in gingival epithelial cell cytoskeletal remodeling and cytokine production.
No sample metadata fields
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