Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 2h in the hypothalamus
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ABSTRACT:
PROVIDER: PRJNA682598 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13198743.fastq.gz | Fastqsanger.gz | |||
| SRR13198744.fastq.gz | Fastqsanger.gz | |||
| SRR13198745.fastq.gz | Fastqsanger.gz | |||
| SRR13198746.fastq.gz | Fastqsanger.gz | |||
| SRR13198747.fastq.gz | Fastqsanger.gz |
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Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162673 | GEO
Project description:Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 6h.
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Project description:Reprogramming of glucocorticoid receptor function by hypoxia: RNA-seq after 24h.
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Project description:Reprogramming of glucocorticoid receptor function by hypoxia: ChIP-seq in the liver.
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Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162155 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE162100 | GEO
Project description:Glucocorticoids (GCs) are the most important stress hormones. They act via the GC receptor GR (encoded by the Nr3c1 gene). Their role is to control metabolic pathways, and to limit inflammation. The latter is often compromised, by unknown mechanisms, in severe inflammatory conditions. We here investigated the in vivo impact of hypoxia on GR function in mice, by genome wide analysis in liver and by means of deep hypoxia. Our data reveal that hypoxia leads to profound reductions in transcriptional output of GR, when stimulated with dexamethasone, leading to absent induction of genes with anti-inflammatory functions such as Tsc22d3 and Dusp1 in liver and other organs. Hypoxia also activates the entire HPA axis, by HIF1α and HIF2α activation in hypothalamus, causing long-term corticosterone production by adrenals. The latter leads to lipolysis in adipose tissue, followed by β-oxidation and ketogenesis in liver, but also to the reprogramming of GR, whereby GR limits its anti-inflammatory functions. These genome-wide RNAseq and ChIPSeq data, accompanied with studies using GR inhibitor, GR mutant mice and adrenalectomized animals suggest that hypoxia leads to increased sensitivity for acute inflammation and lack of protection by dexamethasone, due to the chronic HPA axis stimulation. Our data unfold new physiological pathways, that may have consequences for patients suffering from GC resistance or living at high altitudes.
2021-08-11 | GSE163242 | GEO
Project description:Background: Paediatric obstructive sleep apnoea (OSA) is a highly prevalent sleep disorder resulting in chronic intermittent hypoxia (CIH) that has been linked to metabolism and endocrine impairment. Protein acetylation, which is a frequently occurring posttranslational modification, plays pivotal roles in the regulation of hypothalamic processes. However, the effects of CIH-induced global protein acetylation on hypothalamic function and endocrine metabolism remain poorly understood. Methods: To bridge this knowledge gap, we conducted a study utilizing liquid chromatography–tandem mass spectrometry to analyse the lysine acetylome and proteome of the hypothalamus in healthy infantile mice exposed to 4 weeks of intermittent hypoxia (as a CIH model) compared to normoxic mice (as controls). Results: Our analysis identified and quantified 2699 lysine acetylation sites in 2453 proteins. These acetylated proteins exhibited disruptions primarily in endocrine metabolism, the citrate cycle (TCA cycle), synapse function, and circadian entrainment. Additionally, we observed significant downregulation of proteins that are known to be involved in endocrine hormone secretion. Metabolomic analysis of plasma suggested significant alterations in glycerophospholipid and amino acids metabolism, neuroactive ligand-receptor interaction and serotonergic synapse in children with OSA; these changes may represent potential mechanisms underlying the pathogenesis of OSA in children. Conclusion: This study aimed to elucidate the molecular mechanisms underlying CIH-induced alterations in protein acetylation within the hypothalamus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hypothalamic function, our findings contribute to a deeper understanding of the consequences stemming from CIH-induced changes in protein acetylation within the hypothalamus, as well as its potential role in endocrine impairment.
2024-10-17 | PXD051767 | Pride
Project description:IUGR is associated with an increased risk of obesity in offspring, which is likely driven in part by reprogramming of the hypothalamus due to suboptimal nutrition and hypoxia during development. As such, we performed mRNA-seq on whole hypothalamic tissue to identify altered expression of genes in our model of IUGR and to identify major pathways that could be associated with fetal undernutrition near term.
2020-11-02 | GSE156859 | GEO
Project description:Background Deficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation. Methods To explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system. Findings fdx1b−/− mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b−/− mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients. Interpretation Our study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.fdx1b-/- mutants show a pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b-/- mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients. Our study provides a detailed map of metabolic changes induced by glucocorticoid-deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.
2019-01-21 | GSE107547 | GEO