In vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Using pathway signatures as means of identifying similarities among microarray experiments.
No sample metadata fields
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Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Specimen part
View SamplesThe different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic. We showed that glioma cells are able to progress towards a high-grade phenotype even in immunodeficient mice, albeit more slowly and this progression invariably requires a downregulation of immunostimulatory genes.
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Specimen part
View SamplesThe different phases of tumor immunoediting in vivo were dissected thanks to a murine model of glioma induced by PDGF-B overexpression. We show that low-grade gliomas are highly immunostimulatory and that the adaptive immune system prevents the development of secondary tumor in syngeneic mice. During tumor progression, glioma cells downregulate immunostimulatory genes and the immune infiltrate becomes pro-tumorigenic.
Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
Specimen part
View SamplesThe anthracycline, doxorubicin (Dox), is widely used in oncology, but it may it may cause a cardiomyopathy which has dismal prognosis and cannot be effectively prevented. The secretome of multipotent human amniotic fluid-derived stem cells (hAFS) has previously been demonstrated to reduce ischemic cardiac damage. Here, it is shown that the hAFS conditioned medium (hAFS-CM) antagonizes senescence and apoptosis of cardiomyocytes and cardiac progenitor cells, two major features of Dox cardiotoxicity. Mechanistic studies with primary mouse neonatal cardiomyocytes reveal that hAFS-CM inhibition of Dox-elicited senescence and apoptosis is paralleled by decreased DNA damage and is associated with nuclear translocation of NF-kB and upregulation of a set of genes controlled by NF-kB, namely Il6 and Cxcl1, which promote cardiomyocyte survival, and Cyp1b1 and Abcb1, which encode for proteins involved in Dox metabolism and efflux, respectively. The PI3K/Akt signaling cascade, upstream of NF-kB, is potently activated by the hAFS-CM and pre-treatment with a PI3K inhibitor abrogates NF-kB accumulation into the nucleus, modulation of its target genes, and prevention of Dox-initiated senescence and apoptosis in response to the hAFS-CM. This work may lay the ground for the development of a stem cell-based paracrine therapy of chemotherapy-related cardiotoxicity.
The human amniotic fluid stem cell secretome effectively counteracts doxorubicin-induced cardiotoxicity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging.
Age, Specimen part
View SamplesWe describe a method for isolating RNA suitable for high-throughput RNA sequencing (RNA-seq) from small numbers of fluorescently labeled cells isolated from live zebrafish (Danio rerio) embryos without using costly, commercially available columns. This method ensures high cell viability after dissociation and suspension of cells and gives a very high yield of intact RNA. We demonstrate the utility of our new protocol by isolating RNA from fluorescence activated cell sorted (FAC sorted) pineal complex neurons in wild-type and tbx2b knockdown embryos at 24 hours post fertilization. Tbx2b is a transcription factor required for pineal complex formation. We describe a bioinformatics pipeline used to analyze differential expression following high-throughput sequencing and demonstrate the validity of our results using in situ hybridization of differentially expressed transcripts. This protocol brings modern transcriptome analysis to the study of small cell populations in zebrafish. Overall design: Differential expression analysis of mRNA levels in a single time-point (24 hpf) between wild-type and Tbx2b deficient FAC sorted pineal complex cells
Identification of differentially expressed genes during development of the zebrafish pineal complex using RNA sequencing.
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View SamplesWe elucidate a neurological syndrome affecting both the PNS and CNS defined by CLP1 mutations that impair tRNA splicing Overall design: Identification and biochemical characterization of mutant CLP1 in human patients
Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.
No sample metadata fields
View SamplesArsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung, and bladder cancers, and cardiovascular disease. The mechanisms behind arsenic's effects remain unclear, but recent research indicates that aresnic acts along sex-specific lines and may be an endocrine disruptor. The objective of this study was to evaluate the nature of gene expression chagnes among males and females exposed to arsenic contaminated water in Bangladesh at high and low dose exposures.The median wAs concentration for the low exposure group was 103 g/L for males and 117 g/L for females (range 50200 g/L). For the high exposure group, the median wAs concentration was 355 g /L for males (range 250-500 g /L) and 434 g/L for females (range 2321000 g /L). The PBMCs of males with high exposure compared to those with low exposure there were 534 differentially expressed genes (p <0.05); and for females with high exposure relative to low exposure there were 645 differentially expressed genes (p <0.05) in PBMCs of females.
Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.
Sex, Specimen part
View SamplesThe histone variant macroH2A1 and the poly(ADP-ribose) polymerase PARP-1 both regulate gene transcription by modulating chromatin structure and function. Of the two macroH2A1 splice variants, macroH2A1.1 and macroH2A1.2, the former is often suppressed in cancer and has the unique ability to interact with poly(ADP-ribose). Using ChIP-seq in primary lung fibroblasts, we demonstrate that macroH2A1 is incorporated into either of two spatially and functionally distinct types of chromatin; the first is marked by H3 K27 trimethylation, while the second contains a set of nine histone acetylations. MacroH2A1-regulated genes are involved in cancer progression are specifically found in macroH2A1-containing acetylated chromatin. Through the recruitment of PARP-1, macroH2A1.1 promotes the acetylation of H2B K12 and K120 which plays a key role in the regulation of macroH2A1 target genes in primary cells. The macroH2A1/PARP-1 pathway regulating H2B K12 and K120 acetylation is disrupted in cancer cells, in part, explaining macroH2A1’s role in cancer suppression. Overall design: Three biological replicates of RNA-seq from cells expressing shRNA directed against macroH2A1 or luciferase as a control
MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation.
No sample metadata fields
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