Homo sapiens
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PROVIDER: PRJNA144557 | ENA |
REPOSITORIES: ENA
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Project description:Classically (M1) and alternatively activated (M2) macrophages play distinct roles in various physiological and disease processes. Understanding the gene transcription programs that contribute to macrophage polarization along the M1/M2 spectrum may lead to new tools to detect and therapeutically manipulate macrophage phenotype. Here, we define the M1 and M2 macrophage signature through mRNA microarray. The M1 macrophage signature was defined by 629 up-regulated and 732 down-regulated genes while the M2 macrophage signature was formed by 388 up-regulated and 425 down-regulated genes. While a subset of probes was common to both M1 and M2 cells, others were exclusive to each macrophage subset. The common M1/M2 pathways were characterized by changes in various transcriptional regulators and signaling partners, including increases in Kruppel-like Factor (Klf) 4, but decreases in Klf2. To identify M1 and M2 biomarkers that help discriminate these populations, we selected genes that were increased during M1 or M2 differentiation but decreased in the opposite population. Among top novel M1-distinct genes, we identified CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2). Among top M2 genes, we found early growth response protein 2 (Egr2) and Myc. We validated these genes by Real-Time PCR and developed a CD38/Egr2-based flow cytometry assay that discriminates between M1 and M2 macrophages. Overall, this work defines the M1 and M2 signature and identifies several novel M1 and M2 genes that may be used to distinguish and manipulate M1 and M2 macrophages. Total RNA was prepared from bone marrow-derived macrophages of wild-type mice (n=2-3 independent mice) treated in M0, M1 or M2 conditions (n=2-3 replicates per condition originating from different mice)
2015-12-08 | E-GEOD-69607 | biostudies-arrayexpress
Project description:Prostate cancer is a leading cause of cancer-related deaths of men in the U.S. While localized disease is highly treatable by surgical resection and radiation, cancer that has metastasized remains incurable. Immune cells that primarily scavenge debris, promote prostate cancer angiogenesis and wound repair are M2 Macrophages. They are phenotypically similar to M2 tumor-associated macrophages (M2-TAMs) have been reported to associate with solid tumors and aide in proliferation, metastasis, and resistance to therapy. As an invasive species within the tumor microenvironment, this makes M2-TAMs an ideal therapeutic target in prostate cancer. To identify novel surface antigens expressed on M2-macrophages, we developed a novel method of creating homogenous populations of human macrophages from human CD14+ monocytes in vitro. These homogenous M1 macrophages secrete pro-inflammatory cytokines and our M2 macrophages secrete anti-inflammatory cytokines as well as Vascular Endothelial Growth Factor (VEGF). To identify enriched surface glycoproteins, we then performed solid-phase extraction of N-linked glycopeptides (SPEG) followed by liquid chromatography-tandem Mass Spectrometry (LC-MS/MS) on our homogenous macrophage populations. We discovered novel glycoproteins that are enriched exclusively on human M2-macrophages relative to human M1 macrophages and human CD14+ monocytes. Lastly, we determined if these surface antigens, found enriched on M2 macrophages, were also expressed in human metastatic castrate-resistant prostate cancer (mCRPC) tissues. Using mCRPC tissues from rapid autopsies, we were able to determine M2-macrophage infiltration by using immunohistochemistry and flow cytometry. These findings highlight the presence of macrophage infiltration in human mCRPC but also surface antigens that could be used for prognosis of localized disease and for targeting strategies.
2017-03-31 | PXD005080 | Pride
Project description:Macrophage population in most mammalian organs consists of cells of different origin, with the exception of the central nervous system and the liver, where macrophages of monocytic origin are almost completely absent. The reasons for such distribution and the phenomenon of coexistence of the two separate macrophage lineages with different origin in mammals remain poorly understood. In present study we compared Kupffer cells and monocytes by the immunophenotype, gene expression profile, proteome and pool of mircoRNA. Observed differences do not allow to consider the resident liver macrophages as purely M2 macrophages or monocytes have purely M1 features. Two populations of macrophages of monocytic origin and resident macrophages have fundamentally different roles in maintaining homeostasis. Monocytic macrophages are involved in the regulation of inflammation, and resident macrophages are involved in the regulation of specific organ functions (nitrogen metabolism, complement system protein synthesis). However, if other indicators would be considered as markers of macrophage activity, it is worth noting that Kupffer cells possess some features of M2 macrophages. This is indicated by their expression profile of let-7b/c/d/e miRNAs, a high content of proteins associated with oxidative phosphorylation, as well as an increased level of synthesis of Arg1, IL10.
2021-09-09 | PXD018586 | Pride
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>
2023-09-19 | MTBLS6502 | MetaboLights
Project description:Classically (M1) and alternatively activated (M2) macrophages play distinct roles in various physiological and disease processes. Understanding the gene transcription programs that contribute to macrophage polarization along the M1/M2 spectrum may lead to new tools to detect and therapeutically manipulate macrophage phenotype. Here, we define the M1 and M2 macrophage signature through mRNA microarray. The M1 macrophage signature was defined by 629 up-regulated and 732 down-regulated genes while the M2 macrophage signature was formed by 388 up-regulated and 425 down-regulated genes. While a subset of probes was common to both M1 and M2 cells, others were exclusive to each macrophage subset. The common M1/M2 pathways were characterized by changes in various transcriptional regulators and signaling partners, including increases in Kruppel-like Factor (Klf) 4, but decreases in Klf2. To identify M1 and M2 biomarkers that help discriminate these populations, we selected genes that were increased during M1 or M2 differentiation but decreased in the opposite population. Among top novel M1-distinct genes, we identified CD38, G-protein coupled receptor 18 (Gpr18) and Formyl peptide receptor 2 (Fpr2). Among top M2 genes, we found early growth response protein 2 (Egr2) and Myc. We validated these genes by Real-Time PCR and developed a CD38/Egr2-based flow cytometry assay that discriminates between M1 and M2 macrophages. Overall, this work defines the M1 and M2 signature and identifies several novel M1 and M2 genes that may be used to distinguish and manipulate M1 and M2 macrophages.
2015-12-08 | GSE69607 | GEO
Project description:Recent studies suggest the presence of both âclassically activatedâ M1 and âalternatively activatedâ M2 macrophages in human atherosclerotic tissue, yet due to the lack of validated markers the reported localization patterns of these macrophage phenotypes within plaques are ambiguous. In the present study, we searched for markers that indisputably can identify differentiated M1 and M2 macrophages independently of stimuli that affect the activation status of the two subpopulations. We used these validated markers to assess the presence of M1 and M2 macrophages in different zones of human carotid artery atherosclerotic plaques obtained from 12 patients. Using microarray and qPCR technology we show that the frequently used macrophage subpopulation markers MCP-1 and CD206 do not discriminate between M1 and M2 macrophages. However, we confirm the subtype specificity of the classical M2 marker CD163 and we report that the genes INHBA and DSP (both M1) and SEPP1 and MARCKS (both M2) are highly suitable for macrophage phenotyping. mRNA expression of the pan-macrophage marker CD68 in the shoulder zones of the plaques and in adjacent tissue segments correlated positively with mRNA expression levels of SEPP1, MARCKS and CD163 (r=0.86, 0.94 and 0.96, and r= 0.86, 0.98 and 0.69, respectively) but not with the expression of the M1 markers DSP and INHBA. In contrast, mRNA expression of CD68 in the core of the plaques correlated positively with expression of DSP and INHBA (r=0.73 and 0.49) but not with SEPP1, MARCKS and CD163. These findings suggest that M1 macrophages predominate in the core of human carotid atherosclerotic plaques while M2 macrophages prevail at the periphery of the plaque. Keywords: Expression profiling by array Monocytes from healthy volunteers were differentiated into M1 and M2 macrophages by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating factor (M-CSF), respectively. After 5 days cells were exposed to oxidized LDL. Total RNA was isolated and subjected to gene expression profiling.
2016-06-01 | E-GEOD-22543 | biostudies-arrayexpress
Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4.
2011-09-16 | GSE32164 | GEO
Project description:Study that examines macrophage proteome changes after different preconditioning ('trained macrophages') prior to M1 / M2 activation.
2023-07-20 | PXD036521 | Pride
Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4. Human monocytes were obtained from normal donor buffy coats by two-step gradient centrifugation using Ficoll (Biochrom) and Percoll (Amersham). Non-adherent cells were discarded, and the purified monocytes were incubated for 7 days in RPMI 1640 (Biochom) supplemented with 10% FCS (HyClone) and 100 ng/mL M-CSF to obtain resting macrophages. Macrophage polarization was obtained by removing the culture medium and culturing cells in RPMI 1640 supplemented with 10% FCS and 100 ng/mL LPS plus 20 ng/mL IFN-gamma (M1 polarization) or 20 ng/mL IL-4 (M2 polarization) for 24 h. When needed, chemical inhibitors were added with IL-4.
2011-09-15 | E-GEOD-32164 | biostudies-arrayexpress
Project description:Purpose: To investigate the critical role ER stress exhibit in cellular crosstalk between tumor cells and macrophages in the tumor microenvironment. We performed the two different polarized macrophages under ER stress and harvested the ER-stressed conditioned media. To figure out how two macrophage polarities generated conditioned media impact LLC tumor cells diversely, we use RNA-sequencing (RNA-seq) strategies to profile the deep-sequencing research and find the potential molecular mechanisms during the ER stress transmission from macrophages to tumor cells. The major differential influences the two macrophages proceeded were attribute to macrophages polarization characteristics, which instruct us to study the two polarized macrophages. Hence, we also performed RNA-sequencing during in vitro stimulation of ER stress inducer Tm in two polarized bone marrow derived macrophages. Methods: After different treatment, LLC tumor cells mRNA was extracted and LLC tumor cells transcriptome profiles were generated by deep sequencing, using Illumina. Under ER stress, the different polarized macrophages transcriptome profiles were also generated by deep sequencing, using Illumina. Results: Macrophages displayed different polarization characteristics could respond to ER stress differentially. Notably, GM-BMDMs were more susceptible to ER stress and facilitated the induction of proinflammatory signals, and M-BMDMs facilitate tumor growth, process, and metastasis. LLC cells exhibit different gene expression profiles in response to transferred ER stress from two polarized macrophage populations. Tumor cells that received transmissible ER stress from M2 macrophages has potential to facilitate the tumor survival, while transmissible ER stress from M1 macrophages could lead to more acute cell death and inflammation. Conclusion: Our study revealed that tumor cells could receive the transmissible ER stress from distinct macrophage populations with different extents of ER stress activation in the tumor microenvironment. The proinflammatory M1-like macrophages respond to ER stress more potently and transmit stronger ER stress to tumor cells. By analyzing the secreted components of two ER stressed macrophage populations, we identified that S100A8 and S100A9, which are dominantly secreted by M1-like macrophages, could lead to significant recipient tumor cell death in synergy with transferred ER stress.
2022-12-22 | GSE193669 | GEO