Gene expression profiles of hematopoietic stem/progenitor cells after stimulating CCL2.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE216612 | GEO | 2025/10/26
REPOSITORIES: GEO
Similar Datasets
Project description:Gene-level transcriptome analysis of monocyte mRNA derived from mice that are genetically deficient of the Ccl2 gene or Ccr2 gene The CCL2/CCR2 chemokine axis is critical in monocytes mobilization and innate immunity. Although mice deficient in either gene manifest similar phenotype, such as reduced atherosclerosis, some biologic processes are disrupted in starkly different ways in these mice. We found in a Her2/neu driven mammary carcinoma model, the absence of Ccl2 inhibits tumor growth and prolongs survival, while genetic deletion of Ccr2 has the opposite effect. One of the postulated mechanisms is that Ccl2 and Ccr2 affect monocyte development in different manners. This experiment was designed to compare the whole transcriptome of monocytes that are deficient in either Ccl2 or Ccr2, with the hypothesis that differential development of these monocytes will manifest as differential gene expression profiles.
2016-10-21 | GSE88962 | GEO
Project description:Gene expression profiles of hematopoietic stem/progenitor cells after stimulating CCL2.
| PRJNA894512 | ENA
Project description:Macrophages infiltrating into tumors are known as tumor-associated macrophages (TAMs) and play a central role in tumor progression. In immunohistochemistry, intra-tumoral CD68-positive macrophages correlated with poor prognosis and clinicopathological factors of patients with hepatocellular carcinoma (HCC). Next, we established an indirect co-culture assay between HCC cells and peripheral blood-derived macrophages. cDNA microarray analysis revealed that C-C motif chemokine ligand 2 (CCL2) was highly expressed in HCC cells co-cultured with macrophages. CCL2 bound to CCR2, known as a main receptor of CCL2, and promoted the proliferation and migration of HCC cells and macrophages. The Erk pathway as a downstream signal of the CCL2/CCR2 axis contributed to controlling these phenotypes of HCC cells and macrophages. In the ELISA using serum samples, the serum CCL2 levels of patients with HCC were significantly elevated compared with healthy volunteer donors. The survival outcomes of patients with intra-tumoral CCL2 expression Positive based on immunohistochemistry tended to be worse, without statistical significance. Consequently, the CCL2 upregulated through the interactions between HCC cells and macrophages contributed to HCC progression and the CCL2/CCR2/Erk signal might be an effective candidate for the treatment target of HCC and macrophages.
2024-12-18 | GSE274406 | GEO
Project description:Muscle injury triggers inflammation in which infiltrating mononuclear phagocytes are crucial for tissue regeneration. The interaction of the CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axis that guides phagocyte infiltration is incompletely understood. Here, we show that CX3CR1 deficiency promotes muscle repair and rescues Ccl2-/- mice from impaired muscle regeneration as a result of altered macrophage function, not infiltration. Transcriptomic analysis of muscle mononuclear phagocytes reveals that Apolipoprotein E (ApoE) is up-regulated in mice with efficient regeneration. ApoE treatment enhances phagocytosis by mononuclear phagocytes in vitro, and restores phagocytic activity and muscle regeneration in Ccl2-/- mice. Because CX3CR1 deficiency may compensate for defective CCL2-dependant monocyte recruitment by modulating ApoE-dependent macrophage phagocytic activity, targeting CX3CR1 expressed by macrophages might be a powerful therapeutic approach to improve muscle regeneration.
2015-09-29 | GSE73473 | GEO
Project description:Resident stroma recruits myeloid-derived suppressor cells via CCL2/CCR2 axis in oral squamous cell carcinoma
| PRJNA690228 | ENA
Project description:The pathogenesis of c-MYC and BCL2 double-expressor diffuse large B cell lymphoma (DE DLBCL) remains unclear, particularly in terms of the tumor microenvironment. We aimed to analyze the immune microenvironment of DE DLBCLs to understand the basis of DE-DLBCL's aggressiveness and identify potential therapeutic targets. To discover the key features of DE-DLBCL, fourteen non-DE and 14 DE DLBCL samples underwent RNA-seq analysis. For validation, formalin-fixed paraffin-embedded tissues from 126 patients were immunostained for CD3, CD4, CD8, FOXP3, CD68 and CD163. Two c-MYClow/BCL2low DLBCL (SU-DHL-10 and HT) and 2 c-MYChigh/BCL2high DLBCL cell lines (DOHH2 and OCI-LY8) were used for in vitro assays. The prognostic impact of differential chemokine secretion and immune profiles was evaluated in a mouse tumor model. RNA-seq analysis revealed significantly higher CCL2 and CCR2 mRNA in DE DLBCLs (Padj < 0.05). Public datasets showed higher M2/macrophage ratio and lower T cell infiltration in DE DLBCLs (P < 0.05). Immunohistochemistry confirmed higher M2 macrophages and M2/total macrophage ratio in DE DLBCL (P=0.010 and P=0.098, respectively). In vitro, c-MYChigh/BCL2high cell lines exhibited increased CCL2 secretion, as seen in RNA-seq analysis. Knockdown and overexpression studies identified that MYC and BCL2 overexpression increased CCL2 secretion by upregulation of NF-κB p65 subunit, and the increased CCL2 secretion was crucial for M2 polarization. In mouse tumor models, CCL2 was related to aggressive tumor growth and an immunosuppressive tumor microenvironment. In conclusion, the increased CCL2/CCR2 axis confers aggressiveness of DE DLBCLs by increasing M2 polarization.
2024-09-30 | GSE252690 | GEO
Project description:Leukocyte recruitment, a universal feature of tissue inflammation, is regulated by the interactions of chemokines with their G protein-coupled receptors. Activation of CC chemokine receptor 2 (CCR2) by its cognate chemokine ligands, including CCL2, plays a central role in recruitment of monocytes in several inflammatory diseases. In this study, we used phosphoproteomics to enable unbiased characterization of the signaling network resulting from CCL2 activation of CCR2. Using data-independent acquisition (DIA) mass spectrometry, both the proteome and phosphoproteome were quantified for FlpIn-HEK293T cells stably expressing CCR2, at six time points after activation with CCL2, in comparison with untreated cells. Differential expression analysis identified 699 significantly regulated phosphorylation sites located on 441 proteins. As expected, many of these proteins participate in canonical signal transduction pathways and the regulation of actin cytoskeleton dynamics, including numerous guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). In addition, we identified regulated phosphorylation sites in numerous proteins that exert functions in the nucleus, including several constituents of the nuclear pore complex. This study provides an unprecedented level of detail about CCR2 signalling and identifies potential novel targets for regulation of CCR2 function.
2020-04-08 | PXD015845 | Pride
Project description:In the tumour microenvironment (TME), stroma components play a vital role in tumour development. Myeloid-derived suppressor cells (MDSC) recruited by tumour cells in TME support tumour development. However, the influence of stroma on MDSC is unclear. Here we aimed to unveil the roles of stroma in the recruitment of MDSC in oral squamous cell carcinoma (OSCC). We created xenograft OSCC models on GFP+ bone marrow transplanted nude mice. We co-xenografted human OSCC cells line (HSC-2) with three different types of stromal cells, including human dermal fibroblasts (HDF) or patient-derived stromal cells (PDS1 and PDS2) isolated from two OSCC patients, or without stromal cells. Tumour/stroma co-xenograft models recruited significantly higher numbers of GFP+ bone marrow (BM) cells than the tumour cells alone xenografted group. However, only patient-derived stroma xenograft (PDSX) models promoted GR1/CD11b/Arg1 triple-positive MDSC, which was the main population influenced by stromal character and depended on the stroma secreted CCL2. In vitro inhibition of CCL2 synthesis in PDS cocultures also resulted in significantly decreased migration of BM cells than in HDF coculture and HSC-2 alone culture. Moreover, CCR2+ MDSC infiltrated considerably higher in PDSX models. Taken together, we demonstrated that stromal cells are responsible for MDSC recruitment and stroma secreted CCL2 play an essential role in MDSC recruitment in OSCC.
2021-08-18 | GSE164374 | GEO
Project description:The oral cavity is an easily accessible environment that allows for protective interventions aiming at modulating the immune response to control disease processes driven by a breakdown of host- microbe homeostasis. Periodontal disease (PD) is a prevalent condition in which quantitative and qualitative changes of the oral microbiota (dysbiosis) trigger non-resolving chronic inflammation, progressive bone loss and ultimately tooth loss. Here, we demonstrate the therapeutic benefit of local sustained delivery of the myeloid-recruiting chemokine CCL2 in murine ligature-induced PD using clinically relevant models as a preventive, interventional or reparative therapy. Local delivery of CCL2 into the periodontium inhibited bone loss and accelerated bone gain that could be ascribed to reduced osteoclasts numbers. CCL2 treatment upregulated M2-macrophage and downregulated pro-inflammatory and pro-osteoclastic markers. Furthermore, single cell RNA sequencing indicated that CCL2 therapy reversed disease-associated transcriptomic profiles of murine gingival macrophages via inhibiting TREM-1 signaling in classically activated macrophages and inducing PKA signaling in infiltrating macrophages. Finally, 16S rRNA sequencing showed mitigation of microbial dysbiosis in the periodontium that correlated with a reduction in microbial load in CCL2- treated mice. This study reveals a novel protective effect of CCL2 local delivery in PD as a model for chronic inflammatory diseases caused by a disturbance in host-microbe homeostasis.
2024-08-14 | GSE274721 | GEO
Project description:Scleroderma is a lethal and currently irreversible autoimmune disease characterized by widespread tissue fibrosis and vasculopathy. Using cross-species comparative gene expression profiling we show that murine sclerodematous graft-versus-host disease (sclGVHD) approximates an “inflammatory” subset of human scleroderma and that both diseases demonstrate activation of the IL13 cytokine pathway. We report that both host myeloid cells expressing type I and II activated macrophage markers and graft T-cells produce IL13 and that host mice deficient in either IL13 or IL4Ra, an IL13 signal transducer, are protected from disease. This signaling pathway converges on a single gene, CCL2, which is coordinately upregulated in sclGVHD, in the human inflammatory scleroderma subset and in IL13 treated human dermal fibroblasts. Accordingly, treatment with antibodies to CCL2, and its murine homolog CCL12, prevent sclGVHD. Lastly, we provide evidence that IL13 pathway activation in early scleroderma patients correlates with modified Rodnan skin scores (mRSS). These data indicate that an inflammatory subset of scleroderma is driven by IL13 and may benefit from IL13 or CCL2 blockade. sample vs reference. Total RNA isolated from a time course of primary adult dermal fibroblasts treated with 50nM recombinant IL4 over 24 hours
2011-06-30 | E-GEOD-24409 | biostudies-arrayexpress