scholarly journals Network analysis of transcriptomic diversity amongst resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

PLoS Biology ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. e3000859 ◽  
Author(s):  
Kim M. Summers ◽  
Stephen J. Bush ◽  
David A. Hume
Keyword(s):  
Dendritic Cells ◽  
Network Analysis ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System

scholarly journals Transcriptional network analysis of transcriptomic diversity in resident tissue macrophages and dendritic cells in the mouse mononuclear phagocyte system

2020 ◽  
Author(s):  
Kim M. Summers ◽  
Stephen J. Bush ◽  
David A. Hume
Keyword(s):  
Dendritic Cells ◽  
Network Analysis ◽  
Single Cell ◽  
Cell Types ◽  
Mononuclear Phagocyte ◽  
The Body ◽  
Mononuclear Phagocyte System ◽  
Primary Data ◽  
Analysis Tool ◽  
Rna Seq

AbstractThe mononuclear phagocyte system (MPS) is a family of cells including progenitors, circulating blood monocytes, resident tissue macrophages and dendritic cells (DC) present in every tissue in the body. To test the relationships between markers and transcriptomic diversity in the MPS, we collected from NCBI-GEO >500 quality RNA-seq datasets generated from mouse MPS cells isolated from multiple tissues. The primary data were randomly down-sized to a depth of 10 million reads and requantified. The resulting dataset was clustered using the network analysis tool Graphia. A sample-to-sample matrix revealed that MPS populations could be separated based upon tissue of origin. Cells identified as classical DC subsets, cDC1 and cDC2, and lacking Fcgr1 (CD64), were centrally-located within the MPS cluster and no more distinct than other MPS cell types. A gene-to-gene correlation matrix identified large generic co-expression clusters associated with MPS maturation and innate immune function. Smaller co-expression gene clusters including the transcription factors that drive them showed higher expression within defined isolated cells, including macrophages and DC from specific tissues. They include a cluster containing Lyve1 that implies a function in endothelial cell homeostasis, a cluster of transcripts enriched in intestinal macrophages and a generic cDC cluster associated with Ccr7. However, transcripts encoding many other putative MPS subset markers including Adgre1, Itgax, Itgam, Clec9a, Cd163, Mertk, Retnla and H2-a/e (class II MHC) clustered idiosyncratically and were not correlated with underlying functions. The data provide no support for the concept of markers of M2 polarization or the specific adaptation of DC to present antigen to T cells. Co-expression of immediate early genes (e.g. Egr1, Fos, Dusp1) and inflammatory cytokines and chemokines (Tnf, Il1b, Ccl3/4) indicated that all tissue disaggregation protocols activate MPS cells. Tissue-specific expression clusters indicated that all cell isolation procedures also co-purify other unrelated cell types that may interact with MPS cells in vivo. Comparative analysis of public RNA-seq and single cell RNA-seq data from the same lung cell populations showed that the extensive heterogeneity implied by the global cluster analysis may be even greater at a single cell level with few markers strongly correlated with each other. This analysis highlights the power of large datasets to identify the diversity of MPS cellular phenotypes, and the limited predictive value of surface markers to define lineages, functions or subpopulations.

scholarly journals A transgenic line that reports CSF1R protein expression provides a definitive marker for the mouse mononuclear phagocyte system

2020 ◽  
Author(s):  
Kathleen Grabert ◽  
Anuj Sehgal ◽  
Katharine M. Irvine ◽  
Evi Wollscheid-Lengeling ◽  
Derya D. Ozdemir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System ◽  
Lymphoid Tissues ◽  
Direct Role ◽  
Hematopoietic Stem ◽  
C Terminus ◽  
Monocytes And Macrophages ◽  
Macrophage Populations

AbstractThe proliferation, differentiation and survival of cells of the mononuclear phagocyte system (MPS, progenitors, monocytes, macrophages and classical dendritic cells) is controlled by signals from the macrophage colony-stimulating factor receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters but none is both universal and lineage-restricted. Here we report the development and characterization of a novel CSF1R reporter mouse. A Fusion Red (FRed) cassette was inserted in-frame with the C-terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells (HSC), arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly-expressed in marrow monocytes and common myeloid progenitors (CMP) but significantly lower in granulocyte-macrophage progenitors (GMP). In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations including classical dendritic cells. Whole mount imaging of non-lymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.

scholarly journals African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

2018 ◽  
Vol 9 ◽  
Author(s):  
Benoit Stijlemans ◽  
Patrick De Baetselier ◽  
Stefan Magez ◽  
Jo A. Van Ginderachter ◽  
Carl De Trez
Keyword(s):  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System ◽  
African Trypanosomiasis

Nanoparticles and the Mononuclear Phagocyte System: Pharmacokinetics and Applications for Inflammatory Diseases

2014 ◽  
Vol 10 (1) ◽  
pp. 22-34 ◽  
Author(s):  
Gina Song ◽  
Jennifer Petschauer ◽  
Andrew Madden ◽  
William Zamboni
Keyword(s):  
Inflammatory Diseases ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocyte System
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