Ontology highlight
ABSTRACT:
PROVIDER: PRJNA945802 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Primary objectives: Characterization of the macrophage population subset that is modulated by enteric neurons
Primary endpoints: Characterization of the macrophage population subset that is modulated by enteric neurons via RNA sequencing
| 2538227 | ecrin-mdr-crc
Project description:Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease. To better understand active gene regulation in human macrophages during activation and differentiation in vitro with different stimuli ChIP-sequencing experiments were performed. Enrichment patterns of the permissive histone modification mark trimetylation of histone protein 3 (H3K4me3) and macrophage lineage-specific transcription factor PU.1 were analyzed.
2014-02-13 | E-GEOD-47188 | biostudies-arrayexpress
Project description:In this study, we determined the miRNA expression profile of bovine alveolar macrophages, using next-generation sequencing strategy. On an Illumina HiSeq 2000 machine, we sequenced 8 miRNA libraries, prepared from small RNA fractions of alveolar macrophages isolated from 8 different healthy animals (Bos taurus). From the data, the potential novel miRNAs were predicted, and the expression levels of the known miRNAs were determined. We report that 80 known bovine miRNAs are expressed in bovine alveolar macrophages with >100 reads per million. The most highly expressed miRNA was bta-miR-21, followed by bta-miR-27a. Additionally, one putatively novel bovine miRNA was identified. To our knowledge, this is the first RNA-seq study to profile miRNA expression in bovine alveolar macrophages and provides an important reference dataset for investigating the regulatory roles miRNAs play in this important immune cell type. Examination of bovine alveolar macrophage miRNA profiles, using RNA-seq. Alveolar macrophages were isolated from lung lavages from 8 animals. Small RNA fractions were prepared from the cells using the Qiagen RNeasy Plus mini kit, and miRNA sequencing libraries were prepared using the Epicentre Scriptminer multiplex kit. The sequencing was performed on an Illumina HiSeq 2000 machine.
2013-09-09 | E-GEOD-41138 | biostudies-arrayexpress
Project description:The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. We applied CITE-seq (single-cell RNA-sequencing + cell-surface protein quantification) to bronchoalveolar lavage fluid and peripheral blood cells longitudinally collected from subjects with AHRF to identify novel alveolar monocyte/macrophage subsets, and then validated their identity in an external cohort using flow cytometry. We identified 2 monocyte and 6 macrophage subsets in alveolar samples using CITE-seq data. Some of the subsets had similar transcriptional profiles as those reported in healthy subjects (metallothionein genes) or patients with COVID-19 (LGMN-expressing). We also identified novel subsets with transcriptional signatures that straddled previously reported monocyte and macrophage subsets. We used information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86, and CD44). In the external cohort, we found a higher proportion of CD163/LGMN alveolar macrophages was associated with mortality. We report a parsimonious set of cell-surface proteins that can distinguish alveolar monocyte/macrophage subsets using scalable approaches that can be applied to clinical cohorts.
2023-10-10 | GSE234918 | GEO
Project description:Purpose: The goal of this study is to investigate the alteration of gene expression pattern of alveolar macrophages by allergen challenge in human asthmatics. Method: By using subsegmental bronchial provocation with allergen (SBP-AG) protocol, we obtained BAL fluids, before and 48 hours after allergen challenge in the subjects enrolled in the protocol. Alveolar macrophages were purified from the BAL fluids and total RNA was isolated. Next-generation sequencing data were generated by using the Illumina system. Results: Using an optimized data analysis workflow, we mapped about 75 million sequence reads per sample to the human genome and identified 29,691 transcripts in the macrophage mRNAs. Among them, the change in the expression profiles of 37 transcripts were statistically significant. Conclusions: It has been well accepted that Th2 cytokine enriched environment transforms the phenotype of macrophages into alternatively activated form. However, the details of a genome-wide gene expression profiles of macrophages were not well investigated. Using RNA-seq technology, we provided comprehensive data of macrophage gene expression profiles in allergic lung inflammation. Our data could offer a framework to study biologic functions of alternatively activated macrophage in chronic inflammatory diseases. mRNA profiles of alveolar macrophages obtained from asthmatics, before and after allergen challenge.
2015-04-01 | E-GEOD-65039 | biostudies-arrayexpress
Project description:Disseminated cancer cells reside in the lung alveolar niche where they are exposed to interactions with alveolar macrophages. Here we report singe-cell RNA-sequencing data of lung macrophages from MMTV-HER2 mice at the early stage (16-weeks) harboring single dormant cancer cells and late stage mice (32-weeks harboring metastatic lesions, as well as wildtype control mice. We discovered alveolar macrophage and interstitial macrophage subsets that change in expression profile and frequency between stages. We find majority of the AMs are homeostatic in phenotype, and emergence of inflammatory AM subsets in late-stage MMTV-HER2 mice.
2024-10-01 | GSE278454 | GEO
Project description:Background. Animal models of elastase intratracheal instillation have shown that elastase, unopposed by α-1 antitrypsin (AAT), can induce alveolar hemorrhage with ensuing macrophage inflammation and lung damage. Aim. To identify markers of alveolar hemorrhage and damage using bronchoalveolar lavage (BAL) samples and lung tissue explants from AAT deficient (AATD) subjects. Methods. BAL samples (17 patients, 15 controls) were evaluated for free heme and iron concentrations. Alveolar macrophage (AlvMac) activation patterns were assessed by RNA sequencing and validated in vitro using heme-stimulated monocyte-derived macrophages (MDM). Lung explants (7 patients, 4 controls) were evaluated for iron sequestration patterns, by Prussian blue stain and ferritin immunohistochemistry, and for ferritin iron imaging and elemental analysis by electron microscopy (EM). Tissue oxidative damage was assessed by 8-OHdG immunohistochemistry. Results. BAL showed significantly elevated free heme and iron concentrations at lobar level. BAL macrophage RNA sequencing showed innate proinflammatory activation, consistent with free heme activation. AATD tissue alveolar and interstitial macrophages showed elevated iron and ferritin accumulation in large lysosomes packed with iron oxide cores with degraded ferritin protein cages. AATD explants showed massive oxidative DNA damage in lung epithelial cells and macrophages. Conclusions. Identification of BAL and tissue markers of alveolar hemorrhage, together with the molecular and cellular evidence of macrophage innate pro-inflammatory activation and oxidative damage, consistent with free heme stimulation, provides ex vivo evidence for the pathogenetic role of elastase-induced alveolar hemorrhage AATD emphysema as shown in animal studies.
2023-04-25 | GSE194313 | GEO
Project description:Macrophage activation syndrome (MAS) is a life-threatening cytokine storm syndrome complicating systemic juvenile idiopathic arthritis (SJIA) and driven by IFN-gamma. SJIA and MAS are also associated with an unexplained emerging inflammatory lung disease (SJIA-LD), with our recent work supporting pulmonary activation of IFN-gamma pathways as a pathologic link between SJIA-LD and MAS. Our objective was to mechanistically define the novel observation of pulmonary inflammation in the TLR9 mouse model of MAS. In acute MAS, lungs exhibit mild but diffuse CD4-predominant, perivascular interstitial inflammation with elevated IFN-gamma, IFN-induced chemokines, and alveolar macrophage expression of IFN-gamma-induced genes. Single-cell RNA-sequencing confirmed IFN-driven transcriptional changes across immune and parenchymal lung cell types. Resolution of MAS was associated with increased alveolar macrophage and interstitial lymphocytic infiltration. alveolar macrophage microarrays confirmed IFN-gamma-induced proinflammatory polarization during acute MAS, which switches towards an anti-inflammatory phenotype during MAS resolution. Interestingly, recurrent MAS led to increased alveolar inflammation and lung injury, and reset alveolar macrophagepolarization towards a proinflammatory state. Furthermore, in mice bearing macrophages insensitive to IFN-gamma, both systemic feature of MAS and pulmonary inflammation were attenuated. These findings demonstrate that experimental MAS induces IFN-gamma-driven pulmonary inflammation replicating key features of SJIA-LD, and provides a model system for testing novel treatments directed towards SJIA-LD.
2021-09-12 | GSE169325 | GEO
Project description:Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
2017-06-25 | GSE82158 | GEO