Expression data of the BMDMs from GPS2 WT and MKO mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66874 | GEO | 2016/06/06
SECONDARY ACCESSION(S): PRJNA278147
REPOSITORIES: GEO
Similar Datasets
Project description:GPS2 binding sites in BMDMs can be localized specially in enhancers (H3K27ac) and promoters (H3K27ac, H3K4me3). Upon GPS2 knock-out in BMDMs, de-repression of certain inflammatory genes occur, as accompanied by increased recruitment of H3K27ac and H3K4me3 marks.
2016-06-06 | GSE66774 | GEO
Project description:To compare the inflammatory responses of WT and SIRPα KO macrophage, we performed a complete transcript profiling of WT and SIRPα-KO M1 macrophage using transcriptome sequencing as a discovery platform. SIRPα-KO mice and WT mice were kept under the same condition. BMDMs were produced from WT and SIRPα-KO mice followed by M1 polarization. RNA was then isolated from the same number of BMDMs.
2021-03-19 | GSE169177 | GEO
Project description:Non-proteolytic ubiquitin signaling mediated by K63 ubiquitin chains plays a critical role in multiple pathways converging on NFKB activation that are key to the development and activation of immune cells. However, a complete understanding of how the regulation of ubiquitin signaling affects immune cells development and functionality is still missing. G Protein Suppressor 2 (GPS2) is a multi-functional protein that recently emerged as an important regulator of inflammation and lipid metabolism through inhibition of Ubc13 activity. Here, we have deleted GPS2 in the B cell lineage results and performed RNAseq of WT and KO splenic B cells.
2017-02-08 | GSE92751 | GEO
Project description:Here, we systemically investigated the GPS2 corepressor complex function on cyclooxygenase 1 (Ptgs1) in macrophage M2 activation. We found the inflammatory states changed the DNA topology structure along with the histone modification and the gene expression on Ptgs1 locus. GPS2 related NCOR/SMRT corepressor physically bound to Ptgs1 promoter and enhancer, and depletion of all corepressor subunits caused the basal overexpression of Ptgs1 along with the H3K27ac activation. The corepressor subunits display a conserved function on Ptgs1 expression in M2 activation and this regulation is dependent on STAT6 but not through the direct interaction. We find the GPS2 depletion interferences the DNA accessibility on Ptgs1 locus and promotes the enhancer-promoter interaction and the transcriptional process in M2 activation. We further find the GPS2 depletion caused the recruitments of KDM1A, which specifically demethylated the H3K9me2/3 on Ptgs1 locus. In summary, these findings suggest a new paradigm of the corepressor mediated common gene repression in M2 activation and indicate the potential function of the GPS2/NCOR/SMRT function in the tissue homeostasis and wound healing during Th2-mediated immune responses.
2022-12-14 | GSE184884 | GEO
Project description:Reticuloendothelial macrophages engulf ~0.2 trillion senescent erythrocytes daily in a process called erythrophagocytosis (EP). This critical mechanism preserves systemic heme-iron homeostasis by regulating red blood cell (RBC) catabolism and iron recycling. Although extensive work has demonstrated the various effects on macrophage metabolic reprogramming by stimulation with proinflammatory cytokines, little is known about the impact of EP on the macrophage metabolome and proteome. Thus, we performed mass spectrometry-based metabolomics and proteomics analyses of bone marrow-derived macrophages (BMDMs) before and after EP of IgG-coated RBCs. Further, metabolomics was performed on BMDMs incubated with free IgG to ensure that changes to macrophage metabolism were due to opsonized RBCs and not to free IgG binding. Uniformly labeled tracing experiments were conducted on BMDMs in the presence and absence of IgG-coated RBCs to assess the flux of glucose through the pentose phosphate pathway (PPP). In this study, we demonstrate that EP significantly alters amino acid and fatty acid metabolism, the Krebs cycle, OXPHOS, and arachidonate-linoleate metabolism. Increases in levels of amino acids, lipids and oxylipins, heme products, and RBC-derived proteins are noted in BMDMs following EP. Tracing experiments with U-13C6 glucose indicated a slower flux through glycolysis and enhanced PPP activation. Notably, we show that it is fueled by glucose derived from the macrophages themselves or from the extracellular media prior to EP, but not from opsonized RBCs. The PPP-derived NADPH can then fuel the oxidative burst, leading to the generation of reactive oxygen species necessary to promote digestion of phagocytosed RBC proteins via radical attack. Results were confirmed by redox proteomics experiments, demonstrating the oxidation of Cys152 and Cys94 of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and hemoglobin-β, respectively. Significant increases in early Krebs cycle and C5-branched dibasic acid metabolites (α-ketoglutarate and 2-hydroxyglutarate, respectively) indicate that EP promotes the dysregulation of mitochondrial metabolism. Lastly, EP stimulated aminolevulinic acid (ALA) synthase and arginase activity as indicated by significant accumulations of ALA and ornithine after IgG-mediated RBC ingestion. Importantly, EP-mediated metabolic reprogramming of BMDMs does not occur following exposure to IgG alone. In conclusion, we show that EP reprograms macrophage metabolism and modifies macrophage polarization.
2020-05-27 | PXD017788 | Pride
Project description:The association between hyper-inflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, non-transcriptional role of GPS2 as a guardian against hyperstimulation of TNFA-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNFA target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the non-transcriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis. RNA-sequencing of polyA selected RNA molecules in 293T cells and ChIP-seq of GPS2, TBL1, and NCOR.
2012-03-23 | E-GEOD-35197 | biostudies-arrayexpress
Project description:Obesity-associated lipid overload triggers non-alcoholic fatty liver diseases (NAFLD), which in part may be driven by alterations of regulatory transcription networks and hepatocyte-selective epigenomes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR)/ histone deacetylase 3 (HDAC3) complex, is a central component of such networks and accelerates the progression of non-alcoholic steatohepatitis (NASH). In hepatocyte-specific Gps2 knockout mice, loss of GPS2 alleviated the development of diet-induced steatosis and fibrosis and caused activation of lipid catabolic genes. By determining differential cistromes, epigenomes and transcriptomes in wild-type, single and double knockout mice, we identified the lipid-sensing nuclear receptor PPARa as a direct target of GPS2. We also provide evidence that in hepatocytes, unlike in macrophages, GPS2 acts in concert with the NCOR subunit of the corepressor complex. By analyzing the liver transcriptomes of human patients, we found that GPS2 expression positively correlated with the expression of NASH/fibrosis signature genes. Collectively, our data suggest that the GPS2-PPARa partnership in hepatocytes may influence the development of NASH/fibrosis in mice and in humans.
2019-03-12 | GSE113157 | GEO
Project description:Gene expression from WT and NFAT5 KO primary macrophage cultures. Keywords: Bone-marrow derived macrophages. We analyzed 4 arrays from each condition: unstimulated WT BMDMs, LPS stimulated WT BMDMs, unstimulated KO BMDMs, LPS stimulated KO BMDMs.
2012-01-20 | E-GEOD-26343 | biostudies-arrayexpress
Project description:This experiement aims to know what the differences of protein translation are in the bone marrow derived macro-phages(BMDMs) from WT mice and Elp3 KO mice. We treated the BMDMs with or without IL-4 for 4 hours.
2022-09-12 | PXD033962 | Pride
Project description:To recruit phagocytes, apoptotic cells characteristically release ATP, which functions as a “danger” signal. Here, we found that the culture supernatant of apoptotic cells activated the macrophages to express anti-inflammatory genes such as NR4A and Thbs1. A high level of AMP accumulated in the apoptotic cell supernatant in a Pannexin1-dependent manner. A nucleotidase inhibitor and A2a adenosine receptor antagonist inhibited the apoptotic supernatant-induced gene expression, suggesting AMP was metabolized to adenosine by an ecto-5’-nucleotidase expressed on macrophages, to activate the macrophage A2a adenosine receptor. Intraperitoneal injection of zymosan into AdoR A2a- or Panx1-deficient mice produced high, sustained levels of inflammatory mediators in the peritoneal lavage. These results indicated that AMP from apoptotic cells suppresses inflammation as a “calm down” signal. If apoptotic cells produce “danger” or “anti-danger” signal(s), we rationalized that such signals would activate gene expression in macrophages. To investigate this possibility, we examined the effect of the culture supernatant from apoptotic cells on macrophage gene expression by using microarrays. For mouse BMDMs, bone marrow cells from female C57BL/6J mice at 8 weeks of age were cultured for more than 7 days with DMEM containing 10% FCS supplemented with mouse M-CSF. We used adherent cells as BMDMs in the study. W3 cells, mouse T cell line expressing Fas, were treated with human Fas ligand at 37°C for 30 min to induce apoptosis. The cells were then washed and re-suspended at a concentration of 1 × 107 cells/ml with RPMI containing 1% FCS, and further incubated for 60 min at 37°C. Following Fas ligand treatment, more than 90% of the W3 cells were Annexin V positive, and only small percentage were positive for both Annexin V and propidium iodide (PI). The culture supernatant was collected from apoptotic W3 cells. Next, BMDMs were incubated with medium (BMDMs-Medium) or apoptotic W3 cell supernatant (BMDMs-Apoptotic cell supernatant) for 1 h. Total RNA was extracted from the cells and hybridized on Affymetrix microarrays.
2014-06-24 | E-GEOD-50883 | biostudies-arrayexpress