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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Dendritic cell response to hypoxia and poly I:C

ABSTRACT: Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand). Keywords: Comparison of single and combined treatment Bone marrow derived Dendritic Cells from mice were stimulated under normoxic or hypoxic conditions for 16h with media or poly I:C. Total cellular RNA was harvested, labeled and hybridised to Affymetrix Mouse Gene ST 1.0 GeneChips. Cel files were normalized with RMA.

ORGANISM(S): Mus musculus

SUBMITTER: Roland Lang

PROVIDER: E-GEOD-24995 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Dendritic cell response to hypoxia and poly I:C

Project description:Investigation whether hypoxic stabilization of HIF-1alpha quantitatively or qualitatively modifies the gene expression pattern induced by poly I:C, a TLR ligand that does not induce normoxic HIF-1alpha stabilization on its own (non-HIF-1alpha-stabilizing TLR ligand). Keywords: Comparison of single and combined treatment

2011-06-29 | GSE24995 | GEO

RNA-seq

Project description:Comprehensive analysis of coding and non -coding transcriptome using ribo-depleted total RNA-seq and poly A selected RNA-seq of MCF-7 cells grown in hypoxia and normoxia. Breast cancer cell line (MCF-7) is cultured in normoxic condition (21% O2) and hypoxic condition (1%O2) for 24 hours. Expression of HIF-1alpha and/or HIF-2alpha subunits was suppressed using siRNAs in hypoxic MCF-7 cells. Total RNA was isolated from both hypoxia and normoxia conditions were subjected for ribosomal depleted stand specific RNA-seq and poly A selected RNA-seq

2014-02-10 | E-MTAB-1994 | biostudies-arrayexpress

Single cell RNA-seq from primary ccRCC-patient-derived cell cultures on the 10X genomics platform

Project description:HIF-metagene identifies hypoxic or constitutive HIF activation in scRNA-seq. Hypoxic normal cells have higher HIF-metagene scores than normoxic normal cells, and ccRCC tumour cells (harbouring VHL inactivation) have higher HIF-metagene score than normal cells.

2022-11-15 | GSE200207 | GEO

Camptothecin-miRNA

Project description:DNA Topoisomerase I inhibition by Camptothecin (CPT) derivatives can impair the hypoxia-induced cell transcriptional response. In the present work, we determined molecular aspects of the mechanism of CPT effects on HIF-1alpha activity in human cancer cells. In particular, we provide evidence that low concentrations of CPT, without interfering with HIF-1alpha mRNA levels, can reduce HIF-1alpha protein expression and activity. As luciferase assays demonstrated the involvement of the HIF-1alpha mRNA 3M-^RUTR in CPT-induced impairment of HIF-1alpha protein regulation, we performed microarray analysis to identify CPT-induced modification of miRNAs targeting HIF-1alpha mRNA under hypoxic-mimetic conditions. The selected miRNAs were then further analyzed demonstrating a role for miR-17-5p and miR-155 in HIF-1alpha protein expression after CPT treatments. The present findings establish miRNAs as key factors in a molecular pathway connecting Top1 inhibition and human HIF-1alpha protein regulation and activity, widening the biological and molecular activity of CPT derivatives and the perspective for novel clinical interventions.

2013-12-02 | E-MTAB-2022 | biostudies-arrayexpress

HIF-1alpha and HIF-2alpha ChIP-chip profiling in intestinal epithelial cells

Project description:Intestinal epithelia exist in a uniquely dynamic oxygen tension microenvironment. Adaptive responses to hypoxia in mammalian cells are regulated largely by hypoxia inducible factor (HIF) transcriptional complexes. Functional HIF exists as an obligate alpha/beta heterodimer, comprising both a constitutive subunit (HIF-1beta), and an oxygen-labile regulatory (alpha) component. To date, three regulatory subunits have been identified, namely HIF-1alpha, HIF-2alpha, and HIF-3alpha, with the highest level of sequence homology conserved between HIF-1alpha and HIF-2alpha. Despite their concurrent expression in intestinal epithelial cells, HIF-1 and HIF-2 play non-redundant roles in the regulation of an overlapping but distinct set of gene targets. In this study, we performed ChIP-on-chip analysis of chromatin isolated from hypoxic intestinal epithelia to delineate HIF-1 and HIF-2 specific loci. Comparison of HIF-1alpha ChIP-chip and HIF-2alpha ChIP-chip to map HIF-1- and HIF-2-specific gene targets across the genome.

2013-11-05 | E-GEOD-43108 | biostudies-arrayexpress

Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth

Project description:Mitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient rho0 cells, we found that HIF-1 pathway activation was comparable in slow-growing rho0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo rho0 cells derived from rho0 xenografts exhibited slightly increased HIF-1alpha expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, rho0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1alpha protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment.

2017-01-01 | GSE80320 | GEO

Genome-wide mapping of Hif-1Î± binding sites in zebrafish [ChIP-seq]

Project description:Analysis of the binding sites of Hif-1Î± in both wild-type and von Hippel Lindau mutant zebrafish lines at 4dpf by ChIP linked next generation sequencing. The von Hippel Lindau mutant displays a systemic hypoxic response under normoxic conditions. Results show the extent of Hif-1Î± binding to the genome, and provide a basis for analysis of the transcriptional response to genetically induced hypoxia in zebrafish. Analysis of the DNA binding sites of Hif-1Î± in both wild-type and von Hippel Lindau mutant zebrafish lines at 4dpf. The von Hippel Lindau mutant displays a systemic hypoxic response under normoxic conditions. Results show the extent of Hif-1Î± binding to the genome, and provide a basis for analysis of the dependency of the transcriptional response on Hif-1Î± in conditions of genetically induced hypoxia in zebrafish.

2016-03-22 | E-GEOD-70727 | biostudies-arrayexpress

HIF-1alpha and HIF-2alpha ChIP-chip profiling in intestinal epithelial cells

2013-11-05 | GSE43108 | GEO

Response of Blastocladiella emersonii to hypoxia, iron deprivation and geldanamycin treatment followed by hypoxia.

Project description:Due to its aquatic saprophytic lifestyle, the fungus Blastocladiella emersonii seems to be adapted to low aerated environments and thus can be an interesting model of study of the hypoxic stress response. Iron deprivation, a hypoxia-mimicking stimulus due to HIF-1 stabilization, and geldanamycin, that causes HIF-1 depletion by HSP90 inhibition, are helpful parameters to find an evidence of an oxygen-dependent regulatory mechanism in B. emersonii similar to the metazoan HIF-1 pathway. Direct transcript comparison between cells grown under normoxic conditions (70%sat. O2 in air) and cells submitted to oxygen deprivation (direct and gradual) and iron (II) deprivation. It was also compared transcripts of cells submitted to direct 1-hour hypoxia (1%sat. O2) with cells treated with geldanamycin for 1 hour, followed to 1-hour hypoxia (1%sat. O2). There are at least 3 biological replicates (independent harvest) and 2 technical replicates of each array (L - left and R - right).

2010-06-24 | E-GEOD-17524 | biostudies-arrayexpress

Expression data from Hif-p4h-1 WT vs KO mouse embyonic fibroblasts under normoxic and hypoxic conditions

Project description:The expression of inflammatory genes were downregulated in Hif-p4h-1 KO mouse embryonic fibroblasts both in normoxic and hypoxic condition, whereas the apoptosis regulation genes were upregulated or anti-apoptotic genes were downregulated in Hif-p4h-1 KO mouse embryonic fibroblasts. We used microarray to study the differential expression of genes in Hif-p4h-1 knockout versus WT mouse embryonic fibroblasts

2017-08-02 | GSE83535 | GEO

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