RNA Sequencing in CD11b cells for Quantitative Analysis of WT and myeloid specific NRP2 Knock out transcriptomes in subcutaneous pancreatic tumors
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118501 | GEO | 2018/08/14
REPOSITORIES: GEO
Similar Datasets
Project description:RNA Sequencing in CD11b cells for Quantitative Analysis of WT and myeloid specific NRP2 Knock out transcriptomes in subcutaneous pancreatic tumors
| PRJNA485822 | ENA
Project description:Differentially expressed genes of CD11b+Gr-1+ immature myeloid cells (IMCs) in the bone marrow and colonic tumor setting of histidine decarboxylase (HDC)-KO mice were examined by microarray (Affymetrix Mouse 430.2 array). Myeloid differentiation-related candidate genes were sought to be isolated and functionally studied. Total RNA of HDC-expressing CD11b+Gr-1+ IMCs of bone marrow were extracted from HDC-EGFP and HDC-EGFP/HDC-KO mice (3 mice in each group). CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) of colon tumor were sorted from 10-12 colon tumors of WT and HDC-KO mice (5 mice in each group), and pooled to extract total RNA for microarray studies. Two technical replicates for each of the four groups. Four sets of comparisons were performed to screen for upregulated or downregulated genes in the HDC-KO CD11b+Gr-1+ IMCs or MDSCs (experiment group) compared to the WT group: (1) HDC-expressing CD11b+Gr-1+ IMCs of bone marrow of HDC KO mice compared to bone marrow IMCs of WT mice; (2) CD11b+Gr-1+ MDSCs in tumors of HDC-KO mice compared to WT mice; (3) CD11b+Gr-1+ MDSCs of WT colon tumors compared to IMCs in the WT bone marrow; and (4) CD11b+Gr-1+ MDSCs of colon tumors of HDC-KO mice compared to IMCs in the bone marrow of HDC-KO mice.
2010-12-15 | E-GEOD-23502 | biostudies-arrayexpress
Project description:Bacterial lung infections are associated with strong infiltration of CD11b+ myeloid cells, which limit life-threatening disease, but also severely damage lung tissue. In a murine lung infection model with Streptococcus pneumoniae, we found intrinsic upregulation of CD11b on resident alveolar macrophages. Such CD11b expression was associated with transcriptomic and proteomic adaptations by alveolar macrophages, leading to the identification of specific molecules and pathways that depended on CD11b. In the absence of CD11b, the antimicrobial defense of alveolar macrophages was strongly reduced, and the production of neutrophil-recruiting chemokines was more pronounced. Moreover, CD11b expression limited the infection and prevented excessive alveolar damage. In conclusion, our study provides detailed molecular insights into the alveolar macrophage-specific immune response to Streptococcus pneumoniae lung infection and reveals profound CD11b-dependent alterations that are critical for effective antimicrobial immunity, neutrophil recruitment, and prevention of alveolar damage.
2023-10-08 | PXD035269 | Pride
Project description:To understand the underlying cause for the observed apoptosis in E2f1-3 deficient myeloid cells. We compared gene expression profiles of Cd11b+ sorted myeloid cells isolated from bone marrow of control (E2F1-/- ) and experimental (Mxcre;E2F1-/-2-/-3f/f ) mice. RNA was extracted from Cd11b cells from bone marrow of eight-week-old mice after FACS sorting with FITC- cojugated Cd11b antibody.
2010-12-03 | E-GEOD-25825 | biostudies-arrayexpress
Project description:To determine differential metabolic gene expression in distinct cell populations from subcutaneous MC38 tumors at baseline and in response to rapamycin, tumors from mice treated with vehicle or rapamycin were harvested, reconstituted to single cell suspensions, and flow sorted into cancer cell (CD45-), tumor-associated macrophage (TAM, CD45+ CD11b+ Ly6G- Ly6C lo F4/80 hi), monocytic myeloid-derived suppressor cell (M-MDSC, CD45+ CD11b+ Ly6G- Ly6C hi), CD8 T cell (CD45+ CD3+ CD8a+), and CD4 T cell (CD45+ CD3+ CD8a-) populations. RNA was extracted and transcripts were quantified by the NanoString nCounter Metabolic Pathways Panel.
2021-02-26 | GSE165223 | GEO
Project description:Background: The importance of CD11b/CD18 expression in neutrophil effector functions is well known. Beyond KINDLIN3 and TALIN1, which are involved in the induction of the high-affinity binding CD11b/CD18 conformation, the signaling pathways that orchestrate this response remain incompletely understood. Method: We performed an unbiased screening method for protein selection by biotin identification (BioID) and investigated the KINDLIN3 interactome. We used liquid chromatography with tandem mass spectrometry as a powerful analytical tool. Generation of NB4 CD18, KINDLIN3 or SKAP2 knock out neutrophils was achieved using CRISPR-Cas9 technology and the cells were examined for their effector function using flow cytometry, live cell imaging, microscopy, adhesion or antibody-dependent cellular cytotoxicity (ADCC). Results: Among the 325 proteins significantly enriched, we identified Src Kinase-Associated Phosphoprotein2 (SKAP2), a protein involved in actin polymerization and integrin-mediated outside-in signaling. CD18 immunoprecipitation in primary or NB4 neutrophils demonstrated the presence of SKAP2 in the CD11b/CD18 complex at steady state. Under this condition, adhesion to plastic, ICAM-1 or fibronectin was observed in the absence of SKAP2, which could be abrogated by blocking the actin-rearrangements with latrunculin B. Upon stimulation of SKAP2-deficient neutrophils, adhesion to fibronectin was enhanced whereas CD18 clustering was strongly reduced. This response corresponded with significantly impaired CD11b/CD18-dependent NADPH oxidase activity, phagocytosis and cytotoxicity against tumor cells. Conclusion: Our results suggest that SKAP2 has a dual role. It may restrict CD11b/CD18-mediated adhesion only under resting conditions, but its major contribution lies in the regulation of dynamic CD11b/CD18-mediated actin-rearrangements and clustering as required for cellular effector functions of human neutrophils.
2024-02-16 | PXD048758 | Pride
Project description:Chronic activation of inflammatory pathways and suppressed interferon are hallmarks of immunosuppressive tumors. Previous studies have shown that CD11b integrin agonists could enhance anti-tumor immunity through myeloid reprograming, but the underlying mechanisms remain unclear. Herein we find that CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling and activating interferon gene expression simultaneously. Repression of NF-κB signaling involves degradation of p65 protein and is context independent. In contrast, CD11b agonism induces STING/STAT1 pathway-mediated interferon gene expression through FAK-mediated mitochondrial dysfunction, with the magnitude of induction dependent on the tumor microenvironment and amplified by cytotoxic therapies. Using tissues from phase I clinical studies, we demonstrate that GB1275 treatment activates STING and STAT1 signaling in TAMs in human tumors. These findings suggest potential mechanism-based therapeutic strategies for CD11b agonists and identify patient populations more likely to benefit.
2023-03-21 | GSE220959 | GEO
Project description:Phenotypic transition of myeloid cells into distinct lineages in vivo is important in pathogen response. To monitor immune cell phenotype transitions in vivo, we developed a quantitative temporal in vivo proteomics (QTiPs) platform, performing multiplexed (10-plex) tandem-mass-tag (TMT)-based mass spectrometry on sorted cells collected from their in situ microenvironment during infection. We temporally characterized a poorly understood, virus-driven CD11b+,Ly6G-,Ly6Chigh-low myeloid cell population throughout an acute phase of infection in both the site of infection and bone marrow. QTiPs, in combination with phenotypic, functional and metabolic analyses, elucidated a pivotal role for inflammatory CD11b+,Ly6G-,Ly6Chigh-low cells in anti-viral immune response and viral clearance. Most importantly, the highly time-resolved QTiPs dataset showed the transition of CD11b+,Ly6G-,Ly6Chigh-low cells into M2-like macrophages which displayed increased antigen presentation capacities and bioenergetic demands late in infection. Our QTiPs approach precisely captures myeloid cell-macrophage transition in this population, and it is a novel platform for measuring temporospatial proteome transitions in vivo.
2017-08-09 | PXD005064 | Pride
Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Keywords: Analysis of Cd11b cells from tumor-free and tumor-bearing mice
2006-10-06 | GSE5455 | GEO
Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Experiment Overall Design: Labeled cRNA extracted from a a total of 9 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 3 control samples represented 3 replicates of RNA extracted from Cd11b cells purified from the spleen of tumor-free mice. The 6 samples obtained from tumor-bearing mice represented 3 replicates each of RNA extracted from Cd11b cells purified from the spleen of tumor-bearing mice. Three out of six samples were incubated for 24 hours in complete medium.
2009-04-29 | E-GEOD-5455 | biostudies-arrayexpress