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CSF1R defines the Mononuclear Phagocyte System lineage in human blood in health and disease

ABSTRACT: CSF1R defines the Mononuclear Phagocyte System lineage in human blood in health and disease

PROVIDER: PRJNA679277 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13081460_1.fastq.gz	Fastqsanger.gz
	SRR13081460_2.fastq.gz	Fastqsanger.gz
	SRR13081461_1.fastq.gz	Fastqsanger.gz
	SRR13081461_2.fastq.gz	Fastqsanger.gz
	SRR13081462_1.fastq.gz	Fastqsanger.gz

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CSF1R defines the mononuclear phagocyte system lineage in human blood in health and COVID-19.

Project description:Mononuclear phagocytes defend tissues, present antigens, and mediate recovery and healing. To date, we lack a marker to unify mononuclear phagocytes in humans or that informs us about their origin. Here, we reassess mononuclear phagocyte ontogeny in human blood through the lineage receptor CSF1R, in the steady state and in COVID-19. We define CSF1R as the first sensitive and reproducible pan-phagocyte lineage marker, to identify and enumerate all conventional monocytes, and the myeloid dendritic cells. In the steady state, CSF1R is sufficient for sorting and immuno-magnetic isolation. In pathology, changes in CSF1R are more sensitive than CD14 and CD16. In COVID-19, a significant drop in membrane CSF1R is useful for stratifying patients, beyond the power of cell categories published thus far, which fail to capture COVID-19 specific events. Importantly, CSF1R defines cells which are neither conventional monocytes nor DCs, which are missed in published analysis. CSF1R decrease can be linked ex vivo to high CSF1 levels. Blood assessment of CSF1R+ cells opens a developmental window to the Mononuclear Phagocyte System in transit from bone marrow to tissues, supports isolation and phenotypic characterisation, identifies novel cell types, and singles out CSF1R inhibition as therapeutic target in COVID-19 and other diseases.

| S-EPMC7928847 | biostudies-literature

CSF1R defines the Mononuclear Phagocyte System lineage in human blood in health and disease

Project description:Use of lineage determining receptors as markers for monocytes

2020-11-19 | GSE161738 | GEO

Murine mononuclear phagocyte lineage cells

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Gene expression data from Peyer's patch mononuclear phagocyte system

Project description:PeyerM-bM-^@M-^Ys patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution, ontogeny, lifespan, function and transcriptional profile of PP MPS. We show that monocytes give rise to macrophages and to lysozyme-expressing DC (LysoDC) which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures and, upon TLR7 stimulation, secrete IL-6 and TNF but no IL-10. However, unlike macrophages, LysoDC display a rapid renewal rate, strongly express genes of the MHCII presentation pathway and prime naM-CM-/ve helper T cells for IFNg production. Our results show that in PP, at steady state, monocytes generate both LysoDC and macrophages which display distinct features from their adjacent villus counterparts. 3 replicates of 3 different mononuclear phagocyte subsets have been extracted from Peyer's Patches of WT C57Bl/6 mice: CD11b+ DC, lysoDC and lysoMac. The total RNA of PP-sorted cells from the 3 independent experiments was extracted with a Qiagen micro RNAeasy PLUS kit. Quantity, quality and absence of genomic DNA contamination were assessed with a Bioanalyser (Agilent). Microarray experiments were performed by the Plateforme Biopuces of Strasbourg (France) using the GeneChipM-BM-. Mouse Gene 1.0 ST array.

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Single-cell RNA profiling of mononuclear phagocyte in colorectal cancer

Project description:During mononuclear phagocyte system evolution, monocytes differentiate into pro-tumorigenic TAMs. We used single cell RNA sequencing (scRNA-seq) to analyze the characteristics of mononuclear phagocyte in colorectal cancer

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Mononuclear phagocyte phenotypes in a multiple sclerosis model

Project description:Mononuclear phagocytes are key regulators of both tissue damage and repair in neuroinflammatory conditions such as multiple sclerosis (MS). To examine divergent phagocyte phenotypes in the inflamed central nervous system (CNS) we introduce an in vivo imaging approach combined with RNAseq and proteomics that allows us to temporally and spatially resolve the evolution of phagocyte polarization in a murine MS model. We show that the initial pro-inflammatory polarization of phagocytes is established after spinal cord entry and critically depends on the compartment they enter. Guided by signals from the CNS environment individual phagocytes then switch their phenotype as lesions move from expansion to resolution. Our study thus provides a first real-time analysis of the temporo-spatial determinants and regulatory principles of phagocyte specification in the inflamed CNS.

2019-07-10 | PXD010245 | Pride

Gene expression data from Peyer's patch mononuclear phagocyte system

Project description:Peyer’s patches (PP) are primary inductive sites of mucosal immunity. Defining PP mononuclear phagocyte system (MPS) is thus crucial to understand the initiation of mucosal immune response. We provide a comprehensive analysis of the phenotype, distribution, ontogeny, lifespan, function and transcriptional profile of PP MPS. We show that monocytes give rise to macrophages and to lysozyme-expressing DC (LysoDC) which are both involved in particulate antigen uptake, display strong innate antiviral and antibacterial gene signatures and, upon TLR7 stimulation, secrete IL-6 and TNF but no IL-10. However, unlike macrophages, LysoDC display a rapid renewal rate, strongly express genes of the MHCII presentation pathway and prime naïve helper T cells for IFNg production. Our results show that in PP, at steady state, monocytes generate both LysoDC and macrophages which display distinct features from their adjacent villus counterparts.

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The mononuclear phagocyte system contributes to fibrosis in post-transplant Obliterans Bronchiolitis

Project description:Bronchiolitis Obliterans Syndrome (BOS) is a fibrotic disease heavily responsible for high mortality rates after lung transplantation. Myofibroblasts are primary effectors of this fibrotic process, but their origin is still under debate. The purpose of this work was to identify the precursors of mesenchymal cells responsible for post-transplant airway fibro-obliteration. Lineage-tracing tools were used to track or deplete potential sources of myofibroblasts in the heterotopic tracheal transplantation model. Allografts were analysed by histology, confocal microscopy, flow cytometry or single-cell transcriptomic analysis. BOS explants were evaluated by histology and confocal microscopy. Myofibroblasts in the allografts were recipient-derived. Still, when recipient mice were treated with tacrolimus, we observed rare epithelial-to-mesenchymal transition phenomena and an increase in donor-derived myofibroblasts (P=0.0467), but the proportion of these cells remained low (7%). Hematopoietic cells, and specifically the mononuclear phagocyte system, gave rise to the majority of myofibroblasts found in occluded airways. Ablation of Cx3cR1+ cells decreased fibro-obliteration (P=0.0151) and myofibroblasts accumulation (P=0.0020). Single-cell RNA-sequencing unveiled similarities between myeloid-derived cells from allografts and both murine and human samples of lung fibrosis. Finally, myofibroblasts expressing the macrophage marker CD68 were increased in BOS explants when compared to controls (13% vs 2.3%, P=0.0007). Recipient-derived myeloid progenitors represent a clinically-relevant source of mesenchymal cells infiltrating the airways after allogeneic transplantation. Therefore, therapies targeting the mononuclear phagocyte system could improve long-term outcomes after lung transplantation.

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The mononuclear phagocyte system contributes to fibrosis in post-transplant Obliterans Bronchiolitis

Project description:The mononuclear phagocyte system contributes to fibrosis in post-transplant Obliterans Bronchiolitis

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Gene expression profiling in murine mononuclear phagocyte lineage cells

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