Homo sapiens isolate:hMQL
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA379060 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5341600.fastq.gz | Fastqsanger.gz | |||
| SRR5341610.fastq.gz | Fastqsanger.gz | |||
| SRR5341601.fastq.gz | Fastqsanger.gz | |||
| SRR5341611.fastq.gz | Fastqsanger.gz | |||
| SRR5341602.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 22 |
Similar Datasets
Project description:Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) g or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via multiple members of the nuclear hormone receptor family, including the retinoid X receptors (RXR). It has been also documented that cytokines are able to modulate macrophage responses to lipid signals but the nature of these interactions and the underlying mechanisms of these processes especially at the level of the chromatinized genome are not well understood. Previous work from our laboratory suggested that STAT6 is a facilitator of nuclear receptor mediated transcriptional activity acting at the genome level. This prompted us to investigate genome-wide DNA binding events and the development of cistromes in human CD14+ monocyte-derived macrophages upon exposure to IL-4. We determined the impact of IL-4 on the PU.1, RXR and STAT6 cistromes within the active enhancer regions marked by H3K27-acetylation using chromatin immunoprecipitation followed by deep sequencing and integrated bioinformatics analyses. We found that about 2/3rd of the IL-4 induced STAT6 peaks co-localized with RXR peaks. These STAT6/RXR co-peaks differed at least in part from the non-overlapping RXR peaks regarding the most enriched de novo transcription factor binding motifs. Interestingly, RXR-binding was not regulated at the STAT6/RXR co-bound enhancers following IL-4 stimulation, but differential enhancer interactions were observed between the IL-4/STAT6 and RXR signaling pathways acting in a gene selective manner. Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages.
2017-07-07 | GSE100889 | GEO
Project description:CD14+ human monocytes differentiating into DCs in the presence of IL4 and GM-CSF were treated with agonists for RXR and its partners or vehicle 18 hours after plating (experiment with RXR and permissive partners, donor 1-3) or 14 hours after plating (experiment with nonpermissive partners, donor 4-6). Cells were harvested 12 hours thereafter. Experiments were performed in biological triplicates representing samples from three different donors. In this study all probable RXR-signaling pathways induced by agonists for RXR, LXRs, PPARs, RAR and VDR were identified in differentiating human monocyte-derived dendritic cells.
2010-09-01 | GSE23073 | GEO
Project description:CD14+ human monocytes differentiating into DCs in the presence of IL4 and GM-CSF were treated with agonists for RXR and its partners or vehicle 18 hours after plating (experiment with RXR and permissive partners, donor 1-3) or 14 hours after plating (experiment with nonpermissive partners, donor 4-6). Cells were harvested 12 hours thereafter. Experiments were performed in biological triplicates representing samples from three different donors. In this study all probable RXR-signaling pathways induced by agonists for RXR, LXRs, PPARs, RAR and VDR were identified in differentiating human monocyte-derived dendritic cells. In the experiments, differentiating dendritic cells were treated for 12 hours with one of the following compounds (ligands): vehicle (DMS:EtOH 1:1) LG268 (RXR agonist) 9-cis retinoic acid (9cisRA, agonist of RAR and RXR) GW3965 (LXRalpha/beta panagonist) rosiglitazone (RSG, PPARgamma agonist) GW1516 (PPARdelta agonist) AM580 (RARalpha agonist) 1,25-dihydroxyvitamin D3 (VDR agonist)
2010-09-01 | E-GEOD-23073 | biostudies-arrayexpress
Project description:Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting specific roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive. Here we show that IL-4-mediated macrophage plasticity results in a greatly extended RXR cistrome via the direct and indirect actions of the transcription factor STAT6. Activation of STAT6 leads to chromatin remodeling and RXR recruitment to de novo enhancers. In addition, STAT6 triggers a secondary transcription factor wave, including PPARγ. PPARγ appears to be indispensable for the development of RXR-bound de novo enhancers, whose activities can be modulated in a very restricted manner by the ligands of the PPARγ:RXR heterodimer. Collectively, these data reveal the mechanisms leading to the dynamic extension of the RXR cistrome, identify the lipid-sensing enhancer set of alternatively polarized macrophages and suggest a pervasive ligand-independent mechanism of action of the receptors.
2018-01-01 | GSE107455 | GEO
Project description:Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting specific roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive. Here we show that IL-4-mediated macrophage plasticity results in a greatly extended RXR cistrome via the direct and indirect actions of the transcription factor STAT6. Activation of STAT6 leads to chromatin remodeling and RXR recruitment to de novo enhancers. In addition, STAT6 triggers a secondary transcription factor wave, including PPARγ. PPARγ appears to be indispensable for the development of RXR-bound de novo enhancers, whose activities can be modulated in a very restricted manner by the ligands of the PPARγ:RXR heterodimer. Collectively, these data reveal the mechanisms leading to the dynamic extension of the RXR cistrome, identify the lipid-sensing enhancer set of alternatively polarized macrophages and suggest a pervasive ligand-independent mechanism of action of the receptors.
2018-01-01 | GSE107456 | GEO
Project description:Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting specific roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive. Here we show that IL-4-mediated macrophage plasticity results in a greatly extended RXR cistrome via the direct and indirect actions of the transcription factor STAT6. Activation of STAT6 leads to chromatin remodeling and RXR recruitment to de novo enhancers. In addition, STAT6 triggers a secondary transcription factor wave, including PPARγ. PPARγ appears to be indispensable for the development of RXR-bound de novo enhancers, whose activities can be modulated in a very restricted manner by the ligands of the PPARγ:RXR heterodimer. Collectively, these data reveal the mechanisms leading to the dynamic extension of the RXR cistrome, identify the lipid-sensing enhancer set of alternatively polarized macrophages and suggest a pervasive ligand-independent mechanism of action of the receptors.
2018-02-12 | GSE110464 | GEO
Project description:Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting specific roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive. Here we show that IL-4-mediated macrophage plasticity results in a greatly extended RXR cistrome via the direct and indirect actions of the transcription factor STAT6. Activation of STAT6 leads to chromatin remodeling and RXR recruitment to de novo enhancers. In addition, STAT6 triggers a secondary transcription factor wave, including PPARγ. PPARγ appears to be indispensable for the development of RXR-bound de novo enhancers, whose activities can be modulated in a very restricted manner by the ligands of the PPARγ:RXR heterodimer. Collectively, these data reveal the mechanisms leading to the dynamic extension of the RXR cistrome, identify the lipid-sensing enhancer set of alternatively polarized macrophages and suggest a pervasive ligand-independent mechanism of action of the receptors.
2019-12-19 | GSE142249 | GEO
Project description:The efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics. 24 Human CD14+ monocyte-sorted PBMC samples representing 4 Healthy Volunteers (HV) and 4 Multiple Sclerosis (MS) patients under 3 different treatment conditions. Condition 1 = (-) Phagocystosis (-) Bexarotene. Condition 2 = (+) Phagocystosis (-) Bexarotene. Condition 3 = (+) Phagocystosis (+) Bexarotene.
2015-11-04 | E-GEOD-66988 | biostudies-arrayexpress
Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of monocyte subsets associated with active versus latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical (CD14-CD16+) monocytes isolated from individuals with active TB (at diagnosis and 2 months post treatment), latent TB, as well as from TB negative healthy controls. Overall, we found specific gene signatures for each monocyte subset that could successfully discriminate between individuals with active TB at diagnosis, treated active TB, latent TB and healthy controls.
2023-01-03 | GSE185372 | GEO
Project description:Human monocytes are a heterogeneous cell population consisting of three subsets: classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Intermediate monocytes contribute to inflammation, and their circulating cell counts are increased in many chronic inflammatory diseases, even though the underlying pathways are poorly characterized. We tested in how far epigenetic mechanisms regulate human monocytes heterogeneity in chronic kidney disease, which is a proinflammatory condition of substantial epidemiological importance. By applying next-generation Methyl-Sequencing (Methyl-Seq) we characterized genome-wide DNA methylation within the three monocyte subsets and analyzed the impact of uremia on DNA methylation in differentiating monocytes. We found that each monocyte subset displays a unique phenotype with regards to DNA methylation. Genes with differentially methylated promoter regions in intermediate monocytes were linked to distinct immunological processes, which is in line with results from recent gene expression analyses. In vitro, uremia induced a dysregulation of DNA methylation in differentiating monocytes which affected several transcription factors important for monocyte differentiation (e.g. FLT3, HDAC1, MNT) and led to enhanced generation of intermediate monocytes. As a potential mediator, the uremic toxin and DNA methylation inhibitor S-Adenosylhomocysteine induced shifts in monocyte subsets in vitro, and associated with monocyte subset counts in vivo. In summary, our data support the concept of monocyte trichotomy and the distinct role of intermediate monocytes in human immunity. The shift in monocyte subsets which occurs in chronic kidney disease, a proinflammatory condition of substantial epidemiological impact, may be induced by the accumulation of specific uremic toxins that mediate epigenetic dysregulation.
2015-10-07 | GSE73788 | GEO