E-MTAB-5012
Ontology highlight
ABSTRACT:
PROVIDER: E-MTAB-5012 | ExpressionAtlas | 2016-10-03
REPOSITORIES: ExpressionAtlas
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Project description:We developed a simplified flow cytometry strategy in order to discriminate monocytes and macrophages in the lung of C57BL/6 mice. Using this strategy, we identified autofluorescent F4/80+ CD11c+ alveolar macrophages, non-autofluorescent CD64+Ly-6C- interstitial macrophages and Ly-6Chi monocytes residing in the lung of WT mice. A fraction of these Ly-6Chi monocytes corresponded to classical blood monocytes associated with the lung vasculature, but another fraction did not depend on CCR2, the chemokine receptor required for monocytes to egress from the bone marrow, as a population of lung Ly-6Chi monocytes was also present in the lung of Ccr2-/- mice. A remaining question was whether lung monocytes represented a particular population of monocytes that could be distinguishable from the classical CCR2-dependent blood monocytes. To address this issue, we performed a transcriptomic comparison of Ly-6Chi monocytes recovered from flushed lung of WT mice (â60% of CCR2- dependent classical blood monocytes and â40% of lung monocytes) and Ccr2-/- mice (more than 95% of lung monocytes). In addition, we tested whether exposure to TLR ligands would affect interstitial macrophages, and we compared to transcriptome of IM at steady-state and IM 1 week after administration of 50 µg CpG-DNA intratracheally.
2017-03-01 | E-MTAB-5012 | biostudies-arrayexpress
Project description:Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).
2016-03-02 | E-GEOD-76033 | biostudies-arrayexpress
Project description:We sought to evaluate in an unbiased way the heterogeneity of lung interstitial macrophages and their relationship with alveolar macrophages, lung Ly-6Chi classical monocytes and Ly-6Clo patrolling monocytes, by single cell RNA-Seq.
2019-07-31 | E-MTAB-7678 | biostudies-arrayexpress
Project description:Blood monocytes/macrophages infiltrate the brain after ischemic stroke and critically influence brain injury and regeneration. We investigated stroke-induced transcriptomic changes of monocytes/macrophages by RNA sequencing profiling, using a mouse model of permanent focal cerebral ischemia. Compared to non-ischemic conditions, brain ischemia induced only moderate genomic changes in blood monocytes, but triggered robust genomic reprogramming in monocytes/macrophages invading the brain. Surprisingly, functional enrichment analysis of the transcriptome of brain macrophages revealed significant overrepresentation of biological processes linked to neurovascular remodeling, such as angiogenesis and axonal regeneration, as early as 5 days after stroke, suggesting a previously underappreciated role for macrophages in initiating post-stroke brain repair. Upstream Regulator analysis predicted peroxisome proliferator-activated receptor gamma (PPARγ) as a master regulator driving the transcriptional reprogramming in post-stroke brain macrophages. Importantly, myeloid cell-specific PPARγ knockout (mKO) mice demonstrated lower post-stroke angiogenesis and neurogenesis than wild-type mice, which correlated significantly with the exacerbation of post-stroke neurological deficits in mKO mice. Collectively, our findings reveal a novel repair-enhancing transcriptome in brain macrophages during post-stroke neurovascular remodeling. As a master switch controlling genomic reprogramming, PPARγ is a rational therapeutic target for promoting and maintaining beneficial macrophage functions, facilitating neurorestoration, and improving long-term functional recovery after ischemic stroke.
2019-11-07 | GSE138805 | GEO
Project description:PPARγ is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPARγ, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPARγ as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPARγ agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPARγ deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARγflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPARγ sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense. The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChip® 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 3 to 4 separate times for 3 to 4 biological replicates.
2012-10-03 | E-GEOD-32034 | biostudies-arrayexpress
Project description:The ontogeny of human lung macrophages derived from blood monocytes is poorly understood. In this study, we employed single-cell RNA-sequencing to investigate the heterogeneity of HSPC-derived human lung monocytes and macrophages in the MISTRG humanized mouse model.
2022-11-11 | GSE217722 | GEO
Project description:DNA methylation profiling of tumor-associated macrophages (TAMs), mammary gland macrophages (MGMs), bone marrow-derived monocytes from healthy (BMDM-Hs), and tumor-bearing mice (BMDM-Ts).
2022-11-04 | GSE195706 | GEO
Project description:Transcriptome analysis of five population of Antigen Presenting Cells: inflammatory macrophages, Inflammatory dendritic cells, Cd14+CD16- monocytes, CD14 dim Cd16+ monocytes and BDCA1+ Dendritic cells. We analyzed transcriptomic profiles from 5 differents DC populations: inflammatory DC and macrophages form inflammatory ascites (ovarian cancer, 4 different donors); CD14+CD16- monocytes, CD14dim CD16+ monocytes and BDCA1+ DC (from 3 different healthy donors) using the Affymetrix Human Gene 1.1 ST platform.
2012-11-01 | E-GEOD-40484 | biostudies-arrayexpress
Project description:Neovascular AMD (nAMD) causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1-/- mice display non-classical monocyte and microglia alterations, and increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. While Nr4a1-/- mice are deficient in non-classical monocytes, results are confounded by macrophage hyper-activation. Nr4a1se2/se2 mice lack a transcriptional activator, resulting in non-classical monocyte loss, without macrophage hyper-activation. We subjected Nr4a1-/- and Nr4a1se2/se2 mice to the laser-induced CNV model and performed multi-parameter flow cytometry. We found that both models lack non-classical monocytes, but only Nr4a1-/- mice displayed increased CNV area. Additionally, CD11c+ macrophages were increased in Nr4a1-/- mice. Single-cell transcriptomic analysis uncovered that CD11c+ macrophages were enriched from Nr4a1-/- mice and expressed a pro-angiogenic transcriptomic profile that was disparate from prior reports of macrophage hyper-activation. These results suggest that non-classical monocytes are dispensable during laser-induced CNV, and NR4A1 deficiency shifts the transcriptional profile toward a pro-angiogenic phenotype.
2024-02-28 | GSE239941 | GEO
Project description:Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. Here we showed that ARDS patients were hypoxaemic and monocytopenic within the first 48 hours of ventilation. Monocytopenia was also observed in mouse models of acute lung injury, in which tissue hypoxia drove the suppression of type I interferon signalling in the bone marrow. This impaired monopoiesis, resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of CSF1 in mice with hypoxic lung injury rescued the monocytopenia, altered the nature of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.
2022-08-12 | PXD033151 | Pride