Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD002582
PROVIDER: PRJNA267095 | ENA |
REPOSITORIES: ENA
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Project description:Although Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved in multiple diseases, including BRCA1/2 mutant breast cancer, responses are usually transient thus requiring the development of combination therapies that can capitalize on PARPi activity. We thus explored mechanisms underlying sensitivity and resistance to PARPi using two intrinsically sensitive and resistant syngeneic murine breast cancer models. Our data indicate that the PARPi sensitive tumor model has a high ratio of M1 anti-tumor/M2 pro-tumor macrophages with the M1/M2 ratio being increased by PARPi. In contrast the PARPi resistant tumor model had very low levels of M1 macrophages and thus a low M1/M2 ratio that was not altered by PARPi. Our data indicate that co-transplantation of the PARPi sensitive and the PARPi resistant tumor results in accumulation of M2 macrophages in the sensitive tumor, rendering the sensitive tumor PARPi resistant. C5aR1 and RPS19/C5aR1 signaling is selectively elevated in the M2 macrophages that are associated with PARPi resistance. Strikingly C5aR1 targeting decreased M2 macrophages, while sparing M1 macrophages rendering PARPi resistant tumors sensitive to PARPi. Consistent with the murine data, human breast cancers with high C5aR1 levels have a poor response to immune checkpoint blockade. Thus targeting C5aR1 may represent a therapeutic approach to selectively deplete M2 macropahges and engender sensitivity to PARPi and potentially other therapeutic approaches.
2023-06-30 | GSE215908 | GEO
Project description:Gene expression profiles from murine BALB/c macrophages at the extremes of the M1 and M2 polarized phenotypes
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Project description:Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function. We used microarray to support proteomic data between M1 and M2 macrophages. M1 macrophages are obtained using cell sorting of CD45+MHCII+CD8a-F4/80+ population from C57BL/6J bone marrow cell derived heterogenous cells under GM-CSF conditioning for 7 days. M2 macrophages are differentiated with 20% L929 cell supernatant for 7 days and sorted from CD45+F4/80+CD11b+ population.
2014-11-14 | E-GEOD-63245 | biostudies-arrayexpress
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:Snail1 is a transcriptional factor required for activation of cancer-associated fibroblasts (CAF). In a murine model of mammary gland cancer, mice with Snai1 gene deletion presented a greater survival and differences in macrophage differentiation with fewer M2 macrophages. Snail1 was not expressed in macrophages and in vitro polarization of monocytes towards M1 or M2 phenotypes was not altered by Snai1 gene depletion. In contrast, when macrophages were incubated with Snail1-expressing CAF or with conditioned medium derived from these cells, they exhibited a lower cytotoxic capability than when incubated with Snail1 KO (inactive) CAFs. We compared gene expression of macrophages polarized by CAF WT versus CAF KO-conditioned medium with that promoter by IFN gamma and IL4, classical M1 and M2 inducers, respectively. We observed that, compared to inactive fibroblasts, active CAF specifically upregulated the expression of some M2 genes as Arg1 and also of genes normally reduced in M1 polarization, such as Arg2, although the gene pattern differed from that stimulated by IL4. A complete list of these genes is presented here.
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Project description:This study aims to identify and characterize miRNA expression in aneurysmal smooth muscle cells (SMCs) and M1 and M2 macrophages isolated by laser microdissection from human AAA biopsy samples. The aim of this study was to profile (with microarray technology) miRNAs in M1 and M2 macrophages and Smooth muscle cells (SMCs), isolated by laser capture microdissection (LCM). SMCs isolated from control non-aneurysmal aortas were the control group according to which data were normalized. Areas enriched in M1 macrophages, M2 macrophages and smooth muscle cells were microdissected (9.8 [4.7-16.2] mm2) from two different biopsy samples of human abdominal aortic aneurysm. An area enriched in smooth muscle cells was microdissected from two biopsy samples of non aneurysmal abdominal aortas. Each microdissected samples were analyzed independently on microarray. M1 and M2 macrophages and smooth muscle cells expressed in human abdominal aneurysmal aortas were each analyzed in duplicate (each isolated from different human donors of abdominal aortic aneurysm). Analysis of replicated samples of cells were performed on a second microarray. Data were normalized with smooth muscle cells isolated from human abdominal non aneurysmal aortas.
2014-10-09 | E-GEOD-62179 | 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. 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:Purpose: RNA-sequencing was performed to identify gene expression changes between bone marrow derived macrophages isolated from wildtype and mirn23a-/- (Mirc11-/-) mice that were either M1 or M2 polarized. Results: Diferential gene expression was examined between wildtype and mirn23a-/- M1 polarized macrophages and wildtype and mirn23a-/- M2 polarized macrophages. The number of genes with significant (p<0.05) 2-fold changes in our M1 dataset is 4-fold higher than the 2-fold changed genes in our M2 dataset. 43 unique genes were differentially expressed over 2-fold in M1 mutant macrophages compared to wildtype with 29 upregulated and 14 downregulated. 10 genes (8 downregulated/ 2 upregulated)were differentially expressed in mirn23a-/- M2 macrophages by at least 2-fold compared to wildtype.
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Project description:Monocytes mature to macrophages in the presence of the lineage determining cytokine M-CSF. They can be further polarized into M1 or M2 macrophages with distinct functional properties. We used microarrays to detail the global programme of gene expression underlying macrophage maturation and polarization and identified distinct classes of up-regulated genes during this process. Experiment Overall Design: Freshly isolated monocytes were cultured in the presence of M-CSF for 7 days, and then polarized to M1 or M2 cells. The study includes Monocytes at day 0, macrophages at day 3 and 7, M1 and m2 polarized macrophages.
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Project description:Macrophages have distinct characteristics depending on their microenvironment. We performed proteomic analysis between M1 and M2 macrophages and found that cellular metabolism is the key regulator of macrophage function. We used microarray to support proteomic data between M1 and M2 macrophages.
2014-11-14 | GSE63245 | GEO