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

Summers, Kim M.; Bush, Stephen J.; Hume, David

doi:10.1371/journal.pbio.3000859

Cited by 113 publications

(140 citation statements)

References 194 publications

(331 reference statements)

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“…In the isolated rat macrophages, Cd4 was highly-expressed by BMDM, MDM and PM but just detectable in AM and ESDM. As in mice ( 5 ), Itgam ( Cd11b ) expression was highest in PM. Itgax ( Cd11c ) is still widely considered a dendritic cell (DC) marker in mice, despite clear expression by many tissue macrophage populations [reviewed in ( 48 )].…”

Section: Resultsmentioning

confidence: 77%

“…AM = alveolar macrophages, BMDM = bone marrow derived macrophages, MDM = monocyte derived macrophages, PM = peritoneal macrophages, ESDM = embryonic stem cell derived macrophages. (D) Global enrichment of mouse macrophage AM and PM signature gene sets ( 5 ) in rat AM and PM identified by Gene Set Enrichment Analysis. Rat expression data are ranked according to differential expression in AM or PM compared to all other macrophage populations (indicated by red-blue bars), and the murine AM or PM genesets are mapped onto this profile (black bars) to determine enrichment score (green lines).…”

Section: Resultsmentioning

confidence: 99%

“…We also looked at expression of genes which encode surface markers commonly used to define and separate (sub)populations of mouse macrophages ( 5 , 49 ) (as above). We recently characterised a monoclonal antibody against pig ADGRE1 (F4/80) and found that the antigen was highly-expressed by pig AM ( 50 ).…”

Section: Resultsmentioning

confidence: 99%

“…For comparative analysis of rat and mouse macrophage signatures, we first analysed the enrichment of 12 mouse macrophage signatures identified from cluster analysis of 466 RNA Sequencing datasets, including microglia, lung, Kupffer cells, CCR7 + DC, monocytes, peritoneum, Lyve1 + macrophages, DC, intestinal macrophages, Langerhans cells, cDC1s, and a cluster common to all mononuclear phagocytes ( 5 ), in each rat macrophage population compared to all the others using Gene Set Enrichment Analysis. The mouse AM and PM signatures showed significant enrichment in the rat AM and PM populations, respectively ( Figure 4D ), whereas no significant enrichment was observed for rat ESDM, BMDM, or MDM.…”

Section: Resultsmentioning

confidence: 99%

“…The enrichment of Molecular Signature (MSIG) database Gene Ontology sets, including BP, CC and MF (MSIG collection 5) in each macrophage population compared to the other 4 populations combined was analysed using Gene Set Enrichment Analysis (GSEA, Broad Institute) with phenotype permutation and default settings. For comparative analysis of rat and mouse macrophage signatures, we used GSEA to analyse the enrichment of 12 mouse macrophage signatures identified from cluster analysis of 466 RNA Sequencing datasets (cluster 7-microglia, 10-lung, 12-Kupffer cells, 13-CCR7 + DC, 15-monocytes, 21-peritoneum, 22-Lyve1 + , 28-DC, 38-Intestinal macrophages, 43-Langerhans cells, 49-cDC1s, 3-mononuclear phagocytes) ( 5 )in each rat macrophage population compared to all others.…”

Section: Methodsmentioning

confidence: 99%

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Transcriptomic Analysis of Rat Macrophages

et al. 2021

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The laboratory rat is widely used as a model for human diseases. Many of these diseases involve monocytes and tissue macrophages in different states of activation. Whilst methods for in vitro differentiation of mouse macrophages from embryonic stem cells (ESC) and bone marrow (BM) are well established, these are lacking for the rat. The gene expression profiles of rat macrophages have also not been characterised to the same extent as mouse. We have established the methodology for production of rat ESC-derived macrophages and compared their gene expression profiles to macrophages obtained from the lung and peritoneal cavity and those differentiated from BM and blood monocytes. We determined the gene signature of Kupffer cells in the liver using rats deficient in macrophage colony stimulating factor receptor (CSF1R). We also examined the response of BM-derived macrophages to lipopolysaccharide (LPS). The results indicate that many, but not all, tissue-specific adaptations observed in mice are conserved in the rat. Importantly, we show that unlike mice, rat macrophages express the CSF1R ligand, colony stimulating factor 1 (CSF1).

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Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Transcriptomic Analysis of Rat Macrophages

et al. 2021

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Advances in understanding epigenetic impacts on dendritic cell regulation and function

Verlander

Cummings

Brown

et al. 2022

Clinical and Translational Dis

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Dendritic cells (DCs) are the only cells empowered with inducing primary immune response among resting naïve T lymphocytes, hence it is crucial to understand the regulation and function of DCs. During an adaptive immune response, DCs acquire antigens from invasive entities and present the antigens on their own cell surface, hence they are also known as professional antigen‐presenting cells. Epigenetic modifications to the genome play an important role in both the development and the function of DCs. In this direction, significant advancements have been made using high‐throughput methods like ATAC‐seq, ChIP‐seq, RNA‐seq, bisulfite‐seq and so forth to uncover chromatin accessibility landscape, genome‐wide transcription factor (TF) binding, complete transcriptomic profiles, and DNA methylation, respectively. DCs lineage specification and function are determined by TF binding, which is dependent on epigenetic modifications. However, major gaps in knowledge still exist regarding how and why aberrant epigenetic modifications result in defective development and function of DCs leading to an impaired immune system. Hence, this review compiles up‐to‐date literature regarding the exquisite regulation of DCs via epigenetic regulation, to emphasize the potential of further epigenetics research on DCs for addressing current gaps of knowledge in the field. The review also briefly highlights recent findings on DC defects in coronavirus disease 2019 revealed by single‐cell RNA‐seq, and the importance of DCs in clinical trials. Overall, the review highlights how epigenetics‐based state‐of‐the‐art high‐throughput technology can help discoveries on DCs which are crucial to the immune system and pathogenesis, and how DCs are currently targeted for therapeutic developments and clinical trials.

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Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues

et al. 2022

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This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy and functional characterization of mouse and human dendritic cells (DC) from lymphoid organs and various nonlymphoid tissues.DC are sentinels of the immune system present in almost every mammalian organ. Since they represent a rare cell population, DC need to be extracted from organs with protocols that are specifically developed for each tissue. This article provides detailed protocols for the preparation of single‐cell suspensions from various mouse nonlymphoid tissues, including skin, intestine, lung, kidney, mammary glands, oral mucosa and transplantable tumors. Furthermore, our guidelines include comprehensive protocols for multiplex flow cytometry analysis of DC subsets and feature top tricks for their proper discrimination from other myeloid cells. With this collection, we provide guidelines for in‐depth analysis of DC subsets that will advance our understanding of their respective roles in healthy and diseased tissues.While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer‐reviewed by leading experts and approved by all coauthors, making it an essential resource for basic and clinical DC immunologists.

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

Cited by 113 publications

References 194 publications

Transcriptomic Analysis of Rat Macrophages

Transcriptomic Analysis of Rat Macrophages

Advances in understanding epigenetic impacts on dendritic cell regulation and function

Guidelines for DC preparation and flow cytometry analysis of mouse nonlymphoid tissues

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