Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.
Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.
Sex, Age, Specimen part, Disease, Treatment, Subject
View SamplesRecent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2.
Tripartite motif 24 (Trim24/Tif1α) tumor suppressor protein is a novel negative regulator of interferon (IFN)/signal transducers and activators of transcription (STAT) signaling pathway acting through retinoic acid receptor α (Rarα) inhibition.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
Cell line
View SamplesHeterochromatin-protein 1 (HP1) is a functionally diverse family of proteins. In particular, Drosophila dHP1c forms a complex with the transcription factors WOC and ROW (dHP1EU) that localizes at euchromatin and regulates gene expression.
dDsk2 regulates H2Bub1 and RNA polymerase II pausing at dHP1c complex target genes.
No sample metadata fields
View Samplesaffy_popsec_nancy_roots_poplar - This project aims to identify genes of interest for water deficit acclimation and/or adaptation in a tree species: poplar. We look for genes and gene expression networks related to drought stress. We intend to analyse the transcriptome in root apices, in two genotypes, Carpaccio and Soligo, at various stages and intensities of stress. Root apex is the location of root elongation and these analyses intend to identify genes involved in the control of cell expansion and thus of root elongation. Indeed, root growth maintenance in response to water shortage contributes to plant tolerance to water deficit. The comparison between medium and severe stress intensities and between early and long term stresses will power the selection of genes of interest. The co-analysis of two genotypes of contrasted tolerance to water deficit should help to better discriminate genes presenting a potential adaptative character from genes responding passively to the constraint.-Two poplar clones, Soligo (S) and Carpacio (C) were submitted to 4 treatments: control, mild water deficit, moderate water deficit (12-day long for both) and early-drought stress (about 36-h long). Growth and physiology was characterised on a batch of plants and samples collected on another batch of plants. Four to eight root apices (1cm-long) were collected on each individual tree. Total RNAs were extracted from all roots for each tree individually. Two pools of 3 (or 2) individuals were made using equimolar ratio. A pool is considered as one biological replicate and corresponds to one Affymetrix slide. The two biological replicates originate from the same experiment.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View Samplesaffy_popsec_nancy_leaves_poplar - affy_popsec_nancy_leaves2007_poplar - This project aims to identify genes of interest for water deficit acclimation and/or adaptation in a tree species: poplar. We look for genes and gene expression networks related to drought stress. We intend to analyse the transcriptome in mature leaves, in two genotypes, Carpaccio and Soligo, at various stages and intensities of stress. During water deficit, leaves underwent many processes aiming to maintain cells integrity such as water status adjustment through osmoregulation or cell detoxication. These analyses intend to identify genes of interest involved in homeostasis maintenance. The comparison between medium and severe stress intensities and between early and long term stresses will power the selection of genes of interest. The co-analysis of two genotypes of contrasted tolerance to water deficit should help to discriminate genes presenting a potential adaptative character from genes responding passively to the constraint-In a first experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 4 treatments: control, mild water deficit, moderate water deficit (12-day long for both) and early-drought stress (about 36-h long). Growth and physiology was characterised on a batch of plants and samples collected on another batch of plants. In a second experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 2 treatments: control and moderate water deficit. Mature leaves were collected and total RNAs were extracted from each tree individually. Two pools of 3 (or 2) individuals were made using equimolar ratio. A pool is considered as one biological replicate and corresponds to one Affimetrix slide.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View Samplesaffy_popsec_nancy_leaves_poplar - affy_popsec_nancy_leaves2008_poplar - This project aims to identify genes of interest for water deficit acclimation and/or adaptation in a tree species: poplar. We look for genes and gene expression networks related to drought stress. We intend to analyse the transcriptome in mature leaves, in two genotypes, Carpaccio and Soligo, at various stages and intensities of stress. During water deficit, leaves underwent many processes aiming to maintain cells integrity such as water status adjustment through osmoregulation or cell detoxication. These analyses intend to identify genes of interest involved in homeostasis maintenance. The comparison between medium and severe stress intensities and between early and long term stresses will power the selection of genes of interest. The co-analysis of two genotypes of contrasted tolerance to water deficit should help to discriminate genes presenting a potential adaptative character from genes responding passively to the constraint-In a first experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 4 treatments: control, mild water deficit, moderate water deficit (12-day long for both) and early-drought stress (about 36-h long). Growth and physiology was characterised on a batch of plants and samples collected on another batch of plants. In a second experiment, two poplar clones, Soligo (S) and Carpacio (C) were submitted to 2 treatments: control and moderate water deficit. Mature leaves were collected and total RNAs were extracted from each tree individually. Two pools of 3 (or 2) individuals were made using equimolar ratio. A pool is considered as one biological replicate and corresponds to one Affymetrix slide.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View Samplesaffy_genomic_poplar - affy_genomic_poplar - The project aims to identify genes of interest for water deficit acclimation in poplar. We look for genes and gene expression networks related to drought stress in two hybrid cultivars, differing in their drought tolerance in field. Affymetrix poplar genome array was designed on several Populus species. In order to deal with comparative approaches, we checked the convenience of the array by hybridizing genomic DNA of the two hybrid cultivars (Populus deltoides Populus nigra, namely cv Carpaccio and cv Soligo). This point is important as transcript sequence might have diverged in the two genomes (Fossati et al, 2005), which could lead to absence of hybridization without physiological meaning. -Two poplar cultivars, Soligo (S) and Carpacio (C) were grown in controlled conditions. Mature leaves were collected and genomic DNA was extracted from leaves in CTAB buffer. gDNA was fragmented with DNAse1. DNA fragments were labelled with Biotin N6-ddATP and hybridized on Affymetrix poplar genome array. Two technical replicates per genotype were performed.
Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes.
Specimen part
View SamplesThe transcriptional coregulator Trim24 (formerly known as TIF1a) functions in mice as a liver-specific tumor suppressor. Mice carrying a null mutation in the Trim24 gene all develop hepatocellular carcinoma (HCC).
Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha.
Age
View SamplesWe compared the transcriptome in E16.5 embryonic mouse cortex isolated by microdissection, in control (+/+) mice and in mice with mutation in frizzled3 (Fzd3) and Celsr3. Overall design: Triplicate RNA samples prepared for each genotype
Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling.
Specimen part, Subject
View Samples