Similar Datasets
Project description:Macrophage plasticity allows the adoption of distinct functional states in response to environmental cues. While unique transcriptomic profiles define these states, focusing solely on transcription neglects potential long-term effects. The investigation of epigenetic changes can be used to understand how temporary stimuli can result in lasting effects. Moreover, epigenetic alterations play an important role in the pathophysiology of macrophages, including phenomena related to the trained innate immunity, which allow faster and more efficient inflammatory responses upon subsequent encounters with the same pathogen. In this study, we used a multi-omics approach to elucidate the interplay between gene expression and DNA-methylation, unravelling the long-term effects of diverse polarizing environments on macrophage activity. We identified a common core set of genes that are differentially methylated regardless of exposure suggesting a potential mechanism for rapid adaptation to various stimuli. These conserved epigenetic modifications might represent a fundamental state that allows for flexible responses to various environmental cues. Functional analysis revealed that processes requiring rapid responses displayed transcriptomic regulation, whereas functions critical for long-term adaptations exhibited co-regulation at both transcriptomic and epigenetic levels. Our study unveils a novel set of genes critically linked to the long-term effects of macrophage polarization. This discovery underscores the potential of epigenetics in elucidating how macrophages establish long-term memory and influence health outcomes.
2024-09-18 | GSE273627 | GEO
Project description:The innate immune system safeguards the organism from both pathogenic and environmental stressors. Even physiological levels of nutrients affect organismal and intra-cellular metabolism and challenge the immune system. In the long term, over-nutrition leads to low-grade systemic inflammation. Here, we investigate tissue-resident components of the innate immune-system –macrophages and their response to short-term and long-term nutritional challenges. We analyze the transcriptomes of seven tissue-resident macrophage populations upon metabolic challenge and identify adipose tissue macrophages and the IL-1 pathway as early sensors of metabolic changes. Furthermore, by comparing functional responses between macrophage subtypes, we propose a regulatory, anti-inflammatory role of heat shock proteins of the HSP70 family in response to a metabolic challenge. Our data provides a resource for assessing the impact of nutrition and over-nutrition on the spectrum of macrophages across tissues with a potential for identification of systemic responses.
2020-02-04 | GSE133127 | GEO
Project description:Glioblastoma (GBM) is the most common and malignant type of primary brain tumor in adults and prognosis of most GBM patients is poor. However, a small percentage of patients show a long term survival of 36 mo or longer after diagnosis. Epigenetic profiles can provide molecular markers for patient prognosis: recently, a G-CIMP positive phenotype associated with IDH1 mutations has been described for GBMs with good prognosis. In the present analysis we performed genome-wide DNA methylation profiling of short-term survivors (STS; overall survival < 1 y) and long-term survivors (LTS; overall survival > 3 y) by utilizing the HumanMethylation450K BeadChips to assess quantitative methylation at > 480,000 CpG sites. Cluster analysis has shown that a subset of LTS showed a G-CIMP positive phenotype that was tightly associated with IDH1 mutation status and was confirmed by analysis of the G-CIMP signature genes. Using high stringency criteria for differential hypermethylation between non-cancer brain and tumor samples, we identified 2,638 hypermethylated CpG loci (890 genes) in STS GBMs, 3,101 hypermethylated CpG loci (1,062 genes) in LTS (wild type IDH1) and 11,293 hypermethylated CpG loci in LTS (mutated for IDH1), reflecting the CIMP positive phenotype. The location of differentially hypermethylated CpG loci with respect to CpG content, neighborhood context and functional genomic distribution was similar in our sample set, with the majority of CpG loci residing in CpG islands and in gene promoters. Our preliminary study also identified a set of CpG loci differentially hypermethylated between STS and LTS cases, including members of the homeobox gene family (HOXD8, HOXD13 and HOXC4), the transcription factors NR2F2 and TFAP2A, and Dickkopf 2, a negative regulator of the wnt/?-catenin signaling pathway.
| S-EPMC3592900 | biostudies-other
Project description:Gene expression changes in a winter cultivar of barley in response to short and long term cold treatments ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Ben Trevaskis. The equivalent experiment is BB94 at PLEXdb.] treatment: Non-vernalized (3-replications); treatment: Short-term cold (3-replications); treatment: Vernalized (3-replications); treatment: 1 day post-vernalized (3-replications)
2011-03-08 | E-GEOD-27821 | biostudies-arrayexpress
Project description:High fat feeding impairs skeletal muscle metabolic flexibility and induces insulin resistance, whereas exercise training exerts positive effects on substrate handling and improves insulin sensitivity. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression and DNA methylation. HFD markedly induced expression of immune and inflammatory genes, which was not attenuated by Ex. Conversely, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed a significant association between DNA methylation and gene expression changes were PYGM, which was epigenetically regulated in both groups, and ANGPTL4, which was regulated only following Ex. In conclusion, while short-term Ex did not prevent a HFD-induced inflammatory response, it provoked a genomic response that may protect skeletal muscle from atrophy. These epigenetic adaptations provide mechanistic insight into the gene-specific regulation of inflammatory and metabolic processes in human skeletal muscle.
| S-EPMC5680174 | biostudies-literature
Project description:Gene expression changes in a winter cultivar of barley in response to short and long term cold treatments ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Ben Trevaskis. The equivalent experiment is BB94 at PLEXdb.]
2011-03-08 | GSE27821 | GEO
Project description:Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells.
| S-EPMC8269311 | biostudies-literature
Project description:Experimental evolution is becoming a popular approach to study the genomic selection response of evolving populations. Computer simulation studies suggest that the accuracy of the signature increases with the duration of the experiment. Since some assumptions of the computer simulations may be violated, it is important to scrutinize the influence of the experimental duration with real data. Here, we use a highly replicated Evolve and Resequence study in Drosophila simulans to compare the selection targets inferred at different time points. At each time point, approximately the same number of SNPs deviates from neutral expectations, but only 10% of the selected haplotype blocks identified from the full data set can be detected after 20 generations. Those haplotype blocks that emerge already after 20 generations differ from the others by being strongly selected at the beginning of the experiment and display a more parallel selection response. Consistent with previous computer simulations, our results demonstrate that only Evolve and Resequence experiments with a sufficient number of generations can characterize complex adaptive architectures.
| S-EPMC7540288 | biostudies-literature
Project description:Mycotoxin citrinin (CTN) is a secondary metabolite of fungi, becoming a contaminant widely found in foods, feeds, and fermented health supplements. CTN is known to disrupt microtubule and chromosome arrangement at high dose (50 - 150 μM), but the toxicological effect of CTN long-term exposure has not been clearly studied. To investigate the molecular mechanisms of genotoxic, clastogenic, and carcinogenic effects of CTN, RNA-seq was performed on HEK293 cells exposed to chronic 20 μM CTN treatment (3 days for short-term and 30 days for long-term). The transcriptomic profile may reveal some underlying mechanisms regarding chronic carcinogenic potential of CTN, providing information for risk assessment of CTN-contaminated grains and its commercial food products.
2023-03-01 | GSE218082 | GEO
Project description:Previous studies demonstrated that cells inhibit protein synthesis as a compensatory mechanism for mitochondrial dysfunction. Protein synthesis can be attenuated by 1) the inhibition of mTOR kinase, which results in a decrease in the phosphorylation of S6K1 and 4E-BP1 proteins, and 2) an increase in the phosphorylation of eIF2? protein. The present study investigated both of these pathways under conditions of short-term acute and long-term mitochondrial stress. Short-term responses were triggered in mammalian cells by treatment with menadione, antimycin A, or CCCP. Long-term mitochondrial stress was induced by prolonged treatment with menadione or rotenone and expression of genetic alterations, such as knocking down the MIA40 oxidoreductase or knocking out NDUFA11 protein. Short-term menadione, antimycin A, or CCCP cell treatment led to the inhibition of protein synthesis, accompanied by a decrease in mTOR kinase activity, an increase in the phosphorylation of eIF2? (Ser51), and an increase in the level of ATF4 transcription factor. Conversely, long-term stress led to a decrease in eIF2? (Ser51) phosphorylation and ATF4 expression and to an increase in S6K1 (Thr389) phosphorylation. Thus, under long-term mitochondrial stress, cells trigger long-lasting adaptive responses for protection against excessive inhibition of protein synthesis.
| S-EPMC6727742 | biostudies-literature