Sema6D reverse signaling controls lipid metabolism for macrophage polarization linking mTOR to PPARγ
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE99046 | GEO | 2018/05/20
REPOSITORIES: GEO
Similar Datasets
Project description:Purpose: The goal of this study is to compare downstream genes of Sema6D signaling in LPS plus IFNg stimulated macrophages. Methods: Bone marrow derived macrophage mRNA profiles of 7 weeks of wild type (WT) and Sema6D-/- mice were stimulated by LPS for 4 hrs. Results: According to this comparison, we found that 550 genes were downregulated in Sema6D-/- macrophages than WT macrophages in response to LPS. Conclusions: Our study represents 62 genes were supressed in both M1 and M2 Sema6D-/- macrophage than WT macrophages, suggesting of Sema6D reverse sigaling genes.
2018-05-20 | GSE99047 | GEO
Project description:Sema6D is highly expressed in the brain. We used spatial transcriptional analysis to reveal the roles of Sema6D in the brain.
2024-07-12 | GSE220799 | GEO
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:Semaphorin 6D (Sema6D) have various effects in immune responses. However, the involvement of Sema6D in ILC2 funcions remains unclear. We identified the genes regulated by Sema6D in lung ILC2s during IL-33 induced acute lung inflammation.
2022-08-28 | GSE198659 | GEO
Project description:Obesity-associated insulin resistance is characterized by a state of chronic, low-grade inflammation that is associated with the accumulation of M1 proinflammatory macrophages in adipose tissue. Although different evidence explains the mechanisms linking the expansion of adipose tissue and adipose tissue macrophage (ATM) polarization, in the current study we investigated the concept of lipid-induced toxicity as the pathogenic link that could explain the trigger of this response. We addressed this question using isolated ATMs and adipocytes from genetic and diet-induced murine models of obesity. Through transcriptomic and lipidomic analysis, we created a model integrating transcript and lipid species networks simultaneously occurring in adipocytes and ATMs and their reversibility by thiazolidinedione treatment. We show that polarization of ATMs is associated with lipid accumulation and the consequent formation of foam cell–like cells in adipose tissue. Our study reveals that early stages of adipose tissue expansion are characterized by M2-polarized ATMs and that progressive lipid accumulation within ATMs heralds the M1 polarization, a macrophage phenotype associated with severe obesity and insulin resistance. Furthermore, rosiglitazone treatment, which promotes redistribution of lipids toward adipocytes and extends the M2 ATM polarization state, prevents the lipid alterations associated with M1 ATM polarization. Our data indicate that the M1 ATM polarization in obesity might be a macrophage-specific manifestation of a more general lipotoxic pathogenic mechanism. This indicates that strategies to optimize fat deposition and repartitioning toward adipocytes might improve insulin sensitivity by preventing ATM lipotoxicity and M1 polarization. 15 samples; 2 genotypes and 2 time points
2012-03-22 | E-GEOD-36669 | biostudies-arrayexpress
Project description:Sema6D is highly expressed in the amygdala. We used single nucleus RNA sequencing (snRNA-seq) to analyze the roles of Sema6D in the amygdala.
2024-07-12 | GSE216431 | GEO
Project description:The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNγ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4Rα protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling. Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals
2016-06-29 | E-GEOD-72000 | biostudies-arrayexpress
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:We found that the creatine metabolic pathway was differentially regulated under M1 versus M2 polarizing conditions. In return, creatine could suppress M1 by blocking STAT1 tyrosine phosphorylation while promote M2 by sustaining chromatin accessibility of specific gene loci.
2019-08-06 | GSE110403 | GEO
Project description:We found that the creatine metabolic pathway was differentially regulated under M1 versus M2 polarizing conditions. In return, creatine could suppress M1 by blocking STAT1 tyrosine phosphorylation while promote M2 by sustaining chromatin accessibility of specific gene loci.
2019-08-06 | GSE110395 | GEO