Identifying Macrophage-specific L13a Knockout Transcriptomic Signatures
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE190710 | GEO | 2025/07/02
REPOSITORIES: GEO
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Project description:Identifying Macrophage-specific L13a Knockout Transcriptomic Signatures
| PRJNA788140 | ENA
Project description:Classically activated (M1) macrophages protect from infection but can cause inflammatory disease and tissue damage while alternatively activated (M2) macrophages reduce inflammation and promote tissue repair. Modulation of macrophage phenotype may be therapeutically beneficial and requires further understanding of the molecular programs that control macrophage differentiation. A potential mechanism by which macrophages differentiate may be through microRNA (miRNA), which bind to messenger RNA and post-transcriptionally modify gene expression, cell phenotype and function. The inflammation-associated miRNA, miR-155, was rapidly up-regulated over 100-fold in M1, but not M2, macrophages. Inflammatory M1 genes and proteins iNOS, IL-1b and TNF-a were reduced up to 72% in miR-155 knockout mouse macrophages, but miR-155 deficiency did not affect expression of genes associated with M2 macrophages (e.g., Arginase-1). Additionally, a miR-155 oligonucleotide inhibitor efficiently suppressed iNOS and TNF-a gene expression in wild-type M1 macrophages. Comparative transcriptional profiling of unactivated (M0) and M1 macrophages derived from wild-type and miR-155 knockout (KO) mice revealed an M1 signature of approximately 1300 genes, half of which were dependent on miR-155. Real-Time PCR of independent datasets validated miR-155's contribution to induction of iNOS, IL-1b, TNF-a, IL-6 and IL-12, as well as suppression of miR-155 targets Inpp5d, Tspan14, Ptprj and Mafb. Overall, these data indicate that miR-155 plays an essential role in driving the differentiation and effector potential of inflammatory M1 macrophages. Total RNA was prepared from bone marrow-derived macrophages of miR-155 knockout mice (n=2 independent mice) treated in M0, M1 or M2 conditions (n=2 replicates per condition originating from different mice)
2016-07-15 | E-GEOD-77425 | 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:Glucocorticoids (GCs) are known for their anti-inflammatory potential, which includes macrophage polarization into an anti-inflammatory and tissue remodeling state. GCs are routinely co-administered to cancer patients to alleviate the side effects of chemotherapy. However, it is not well known if GCs can modulate tumor-associated macrophages (TAMs) to promote tumor progression. Here, we show that dexamethasone (DEX) induces dose-dependent differentiation of THP-1 monocyte-derived anti-tumorigenic (M1) macrophages into pro-tumorigenic (M2-like) macrophages, even in the presence of M1 cues, and that DEX can repolarize fully differentiated M1 macrophages into an M2-like state. These macrophages have a cytokine profile similar to the pro-tumorigenic (M2) macrophages and can stimulate the proliferation and invasion of triple-negative breast cancer (TNBC) cells in vitro. DEX treatment of an orthotopic mouse model of TNBC attenuated paclitaxel-mediated tumor growth inhibition, increased M2-like TAMs in primary tumors, and enhanced lung metastasis. Transcriptomic analysis of DEX-treated M1 macrophages revealed not only transcriptomic overlap to M2 macrophages, but to human breast cancer TAM transcriptomic data and further to a specific TAM signature associated with aggressive estrogen receptor-negative breast cancer. Our study illustrates a remarkable macrophage repolarization plasticity upon DEX exposure and warrants care in prescribing high doses of GCs to breast cancer patients, especially to those considered for chemotherapy.
2025-03-05 | GSE290519 | 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
Project description:Macrophages are the main effector cells of inflammatory response and play an important role in the initiation and regression of inflammation. Macrophages are derived from monocytes which are differentiated into M1 macrophages (classically activated macrophages) or M2 macrophages (selectively activated macrophages) in response to different external stimuli, distinguished by the differential expression of cytokines, cell surface markers, and chemokines. In vitro macrophages are crucial models for understanding the regulatory mechanism of immune response and the establishment of infection models, ultimately, for the diagnosis or treatment of a variety of diseases. Porcine is the most important agricultural animal and one of the most valuable animal models for preclinical studies, but no unified method for porcine macrophage isolation and differentiation at present, neither a systematic study compared the porcine macrophage obtained by different methods. In this study, we used two strategies to induce porcine BMDM into M1 and two strategies to induce porcine BMDM into M2 macrophages. Subsequently, we compared the transcriptomic profile of BMDM treated with different induction methods by RNA-seq. The DEG analysis showed that porcine M1 macrophage and porcine M2 macrophage obtained have consistent gene signatures as mouse and human macrophages, respectively. We also observed differences in transcriptional levels in macrophages induced by different methods. We obtained the transcriptome sequencing data of macrophages infected by different pathogens from GEO and analyzed them quantitatively. We performed GSEA analysis on macrophages infected with different pathogens and porcine bone marrow-derived macrophages (BMDM). We found that the enrichment pathways of macrophages obtained by different induction methods and macrophages infected by different pathogens were different. Our study provided a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including porcine reproductive and respiratory syndrome virus (PRRSV), African swine fever virus (ASFV), and Toxoplasma gondii.
2025-05-03 | GSE202115 | 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:To investigate the cooperative function Ets1 in macrophage, we generats Ets1 knockout mice.We then performed gene expression profiling analysis in macrophages seperated from either control or ko mice. We also performed Ets1 ChIP-seq, using M1 and M2 macrophages seperated from wild type C57 bone marrow, for mechanism study.
2024-10-01 | GSE271032 | GEO
Project description:Identification of the difference in responsiveness to interleukin-1alpha between M1 and M2 macrophage phenotypes. To identify the difference in responsiveness to interleukin-1alpha between M1 and M2 macrophage phenotypes, we performed micorarray analysis of gene expression in two phenotypes with or without the treatment of interleukin-1alpha.
2014-09-21 | E-GEOD-53680 | biostudies-arrayexpress