ChIP-seq analysis to understand the mechanistic role of NCoR1 as a tolerogenic program suppressor in dendritic cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA433709 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We found in our study that NCoR1 knock down dendritic cells (DCs) develop tolerogenic behavior upon activation and these cells have the potential to modulate T helper cell differentiation toward Treg phenotype. Here to understand the mechanism of this process we performed NCoR1 ChIP-seq in wild type DCs before and after CpG ligand activation and transcriptome analysis of NCoR1 KD DCs to identify the direct and indirect target genes. We also predicted PU.1 as the recruting factor for NCoR1 in DCs based on motif enrichment and later on validated that by performing PU.1 ChIP-seq in control and NCoR1 KD DCs.
2019-10-18 | GSE110421 | GEO
Project description:RNA-seq and ChIP-seq analysis to understand the mechanistic role of NCoR1 as a tolerogenic program suppressor in dendritic cells
| PRJNA433674 | ENA
Project description:In this study, we focused on demonstrating the metabolic aspect of NCoR1 in the regulation of dendritic cells (DCs) functionality. We report that NCoR1 deficient tolerogenic DCs meet their anabolic requirements through enhanced glycolysis and OxPhos, supported by FAO-driven oxygen consumption. Furthermore, individual and dual inhibition of glycolysis through HIF-1α inhibitor (KC7F2) and fatty acid oxidation through CPT1 inhibitor (etomoxir) significantly impaired the secretion of tolerogenic cytokines. To validate the same at the global mRNA level we did bulk RNA-seq to determine the differentially expressed genes in control and NCoR1 KD 6h CpG activated DCs with and without inhibitor treatment.
2024-01-01 | E-MTAB-12066 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-10-18 | GSE110423 | GEO
Project description:Purpose: The goals of this study to dissect mechanism by which NCoR1 regulate expression of diiferent genes at transcriptional level in CD8a+ Dendritic cells. Methods: mRNA expression of Control(Empty) and knockdown (NCoR1+/−) before and after CpG and pIC activation were generated by deep sequencing, in duplicate, using Illumina NextSeq 500 . The sequence reads that passed quality filters were analyzed at the transcript level with two methods:TopHat followed by Cufflinks. Results: we mapped raw reads to the mouse genome (build mm10) with TopHat. Differential expression study was carried out using Cufflinks v2.2.1 and list were filtered using fold change cut-off of 2 and q value <0.05. Conclusions: We found in our study that NCoR1 knock down dendritic cells (DCs) develop tolerogenic behavior upon activation and these cells have the potential to modulate T helper cell differentiation toward Treg phenotype. Here to understand the mechanism of this process we performed NCoR1 ChIP-seq in wild type DCs before and after CpG ligand activation and transcriptome analysis of NCoR1 KD DCs to identify the direct and indirect target genes. We also predicted PU.1 as the recruting factor for NCoR1 in DCs based on motif enrichment and later on validated that by performing PU.1 ChIP-seq in control and NCoR1 KD DCs.
2019-10-18 | GSE110422 | GEO
Project description:Transcriptional profiling of human dendritic cells (DC) comparing control (DC generated with GM-CSF plus IL-4) with three different treatments of tolerogenic (DC generated with GM-CSF plus IL-4 and IL-10, or IL-4, IL-10, and IL-6, or IL-4, IL-10, and TGF-b1) Three two-condition experiments, control (N) vs tolerogenic DC with three different treatments. Pool of 4 indivuduals for each condition. One replicate per array.
2009-11-12 | E-GEOD-18921 | biostudies-arrayexpress
Project description:In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases. Gene expression of a total of 20 gastrocnemius samples from control (CON, n = 5), NCoR1 muscle-specific knockout (NCoR1 MKO, n = 5), wild type (WT, n = 5) and PGC-1alpha muscle-specific transgenic (PGC-1alpha mTg, n = 5) adult male mice was analyzed using GeneChip® Gene 1.0 ST Array System (Affymetrix). NCoR1 MKO and PGC-1alpha mTg samples were compared to CON and WT samples, respectively.
2013-01-08 | E-GEOD-40439 | biostudies-arrayexpress
Project description:RNA-seq was performed to understand the role of NCoR1 in CD8α+ DCs. MutuDC cell line was transduced with empty and Ncor1 shrna lentiviral particles and cells were prepared in unstimulated, 2hr and 6hr (IFNg, pIC and CpG+pIC+IFNg) stimulation condition.
2022-09-20 | E-MTAB-10989 | biostudies-arrayexpress
Project description:Human monocyte-derived dendritic cells (moDCs) have been used as an in vitro model for studying tolerance and immunity. However, the underlying metabolic states of tolerogenic (dexamethasone and vitamin D3-treated), immature and immunogenic (mature, LPS-treated) moDCs have not been completely characterized. Through transcriptomic analyses, we determined that tolerogenic moDCs exhibit augmented catabolic pathways with respect to oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO) and glycolysis. Functionally, tolerogenic moDCs showed the highest mitochondrial membrane potential, production of reactive oxygen species and superoxide, and increased mitochondrial spare respiratory capacity. Tolerogenic and mature moDCs manifested differential FAO gene expression with FAO activity being significantly higher in tolerogenic and immature moDCs than in mature. In addition, tolerogenic and mature moDCs demonstrated similar levels of glycolytic rate, but not glycolytic capacity and reserve, which were more pronounced in tolerogenic and immature moDCs. Finally, tolerogenic and immature moDCs, but not mature moDCs, showed high plasticity to compensate the intracellular ATP content after inhibition of different energetic metabolic pathways. Overall, tolerogenic moDCs exhibit a metabolic signature of increased, stable OXPHOS programing and high plasticity for metabolic adaptation. These findings provide a framework for future research of metabolic properties of human DCs. Total RNA of sixteen samples from four moDC types (tolerogenic, LPS-tolerogenic, immature and mature) were extracted by Trizol (Invitrogen) followed by a clean-up procedure using RNeasy Micro Kit (Qiagen). All RNA samples had an integrity number ≥9.6 assessed by Agilent Bioanalyzer. Total RNA samples were amplified using TargetAmp™ and the biotinilated cRNA was prepared by Nano-g™ Biotin-aRNA Labeling Kit for the Illumina® System (Epicentre). After the hybridization to the Illumina Human HT-12 v4 Beadchips for 17 h at 58°C, the arrays were washed, stained (Illumina Wash Protocol) and then scanned using BeadArray Scanner 500GX. Array data were extracted at the probe level without background correction using Illumina GenomeStudio software. These raw data were quantile normalized and log2 transformed. Technical replicates were obtained from the hybridization in duplicate of three samples. Pearson correlation analysis showed high correlation between the technical replicates (r>0.99). Differentially expressed genes (DEGs) were identified using Limma16 with Benjamini-Hochberg multiple testing correction (p<0.05). DEGs were further clustered into different groups according to the patterns of expression change among the different moDC types using STEM software17. The analysis was performed in R v.2.12.2 (http://www.R-project.org) with Bioconductor 2.12 (http://www.bioconductor.org) and enabled by Pipeline Pilot (www.accelrys.com).
2015-05-08 | E-GEOD-52894 | biostudies-arrayexpress
Project description:Understanding the molecular mechanisms that initiate and control immunosuppression by myeloid cells is essential to overcoming the myeloid-induced disbalance of the immune system observed in patients. Myeloid cells are implicated in aggravated suppression of immunity as seen in cancer as well as in defective modulation of immune responses as observed in autoimmunity. Therefore, signaling pathways controlling immunomodulation by myeloid cells are an attractive target to potentially restore immune homeostasis and increase clinical benefit for a large number of patients. Here, we used label-free quantitative proteomics to identify proteins that are differentially expressed between different myeloid cells (myeloid-derived suppressor cells (MDSCs), tolerogenic dendritic cells (TolDCs), monocyte-derived dendritic cells (MoDCs) and precursor monocytes.
2023-09-20 | PXD027715 | Pride