Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of blocking GSK3 on the gene expression profile in GM-CSF-primed human monocyte derived macrophages. GSK3 inhibition skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
Project description:The functional versatility of macrophages is intrincately tied to factors such as their ontogeny and the specific tissue and extracellular environment. Monocyte-derived macrophages are oppositely instructed by M-CSF or GM-CSF. GM-CSF drives monocyte-derived macrophages towards heightened pro-inflammatory activity and the acquisition of the lung alveolar macrophage phenotype and gene profile whereas M-CSF gives rise to anti-inflammatory, pro-resolving, and immunosuppressive monocyte-derived macrophages. We explored the molecular impact of siRNA mediated knocking-down GSK3A, GSK3B or both (GSK3A/B) on the gene expression profile of GM-CSF-primed human monocyte derived macrophages. GSK3A/B knowdown skewed the transcriptional profile of GM-MØ towards an anti-inflammatory phenotype.
Project description:Identification of genes differentially expressed between human CD14+CD16- and CD16+ monocyte-derived macrophages generated in the presence of either GM-CSF (termed GM14 and GM16, respectively) or M-CSF (termed M14 and M16, respectively)
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. One-carbon metabolism (OCM) is a complex network of biosynthetic pathways that includes de novo biosynthesis of purines and thymidylate, amino acid metabolism, and methylation reactions. We explored the molecular impact of blocking OCM with the anti-folate pemetrexed (PMX) on the gene expression profile in GM-CSF-primed human monocyte derived macrophages.
Project description:Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. GM-CSF drives the generation of human monocyte-derived macrophages with a potent pro-inflammatory activity upon stimulation. Janus Kinase (JAK) inhibitors are small molecules that reversibly inhibit JAK activity and their subsequent intracellular signaling and have become the treatment of choice for diseases with an inflammatory or immune basis. We explored the molecular impact of blocking GM-CSFR-JAK2-STAT5 axis with the Janus Kinase (JAK) inhibitors Upadacitinib or Baricitinib on the gene expression profile in GM-CSF-primed human monocyte derived macrophages.
Project description:Identification of genes differentially expressed between human monocyte-macrophages generated in the presence of either GM-CSF (termed M1) or M-CSF (termed M2)
Project description:This study aims to characterize the transcriptional profile of Granulocyte-macrophage colony-stimulating factor induced macrophages (GM-MÃ) and M-CSF macrophages (M-MÃ) and to investigate in situ a subset of genes and their products specific to each phenotype in human atherosclerosis plaques 18 RNG/MRC two-colour oligonucleotide microarrays (Le Brigand et al. 2006) were used to generate global mRNA expression profiles for GM-CSF-induced, M-CSF-induced, and peritoneal macrophages. The microarray experiments were conducted either as a common reference (peritoneal-like macrophages) design or using a direct design by hybridizing Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-MÃ) and CSF-induced human monocyte-derived macrophages(M-MÃ) on the same arrays
Project description:Comparison of the transcriptome macrophages derived from CD14+ human monocyte-derived macrophages generated in the presence of M-CSF (M-Mphage) or GM-CSF (GM-Mphage) and MTX.
Project description:<p>Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. <em>In vitro</em> macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1-and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM-and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for <em>in vitro</em> macrophage studies. </p>
