ADGRE1 (EMR1, F4/80) Is a Rapidly-Evolving Gene Expressed in Mammalian Monocyte-Macrophages

Waddell, Lindsey; Lefèvre, Lucas; Bush, Stephen J.; Raper, Anna; Young, Rachel; Lisowski, Zofia M.; McCulloch, Mary E. B.; Muriuki, Charity; Sauter, Kristin A.; Clark, Emily L.; Irvine, Katharine M.; Pridans, Clare; Hope, Jayne; Hume, David

doi:10.3389/fimmu.2018.02246

Cited by 98 publications

(99 citation statements)

References 80 publications

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“…CX3CR1 is responsible for synapse elimination (Lee & Chung, 2019;Paolicelli et al, 2011). Circadian expressional changes of mRNA were investigated every 4 hr (Figure 1c), demonstrating that the maximum expression of mRNA for MMPs, F4/80, a macrophage/activated microglia specific protein (Sun et al, 2013;Waddell et al, 2018), MFG-E8, complements was observed at ZT0. mRNA for eat-me signal related molecules, growth arrest-specific protein 6 (GAS6) and protein S, both of which are ligands for MerTK (Brown & Neher, 2014), was expressed at the highest at ZT20.…”

Section: Circadian Changes In Expression Of Synaptic and Microglialmentioning

confidence: 93%

Phagocytic elimination of synapses by microglia during sleep

Choudhury

Miyanishi

Tamano

et al. 2019

Glia

103

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Synaptic strength reduces during sleep, but the underlying mechanisms of this process are unclear. This study showed reduction of synaptic proteins in rat prefrontal cortex (PFC) at AM7 or Zeitgeber Time (ZT0), when the light phase or sleeping period for rats started. At this time point, microglia were weakly activated, displaying larger and more granular somata with increased CD11b expression compared with those at ZT12, as revealed by flow cytometry. Expression of opsonins, such as complements or MFG‐E8, matrix metalloproteinases, and microglial markers at ZT0 were increased compared with that at ZT12. Microglia at ZT0 phagocytosed synapses, as revealed by immunohistochemical staining. Immunoblotting detected more synapsin I in the isolated microglia at ZT0 than at ZT12. Complement C3‐ or MFG‐E8‐bound synapses were the most abundant at ZT0, some of which were phagocytosed by microglia. Systemic administration of synthetic glucocorticoid dexamethasone reduced microglial size, granularity and CD11b expression at ZT0, resembling microglia at ZT12, and increased synaptic proteins and decreased the sleeping period. Noradrenaline (NA) suppressed glutamate‐induced phagocytosis in primary cultured microglia. Systemic administration of the brain monoamine‐depleting agent reserpine decreased NA content and synapsin I expression in PFC, and increased expression of microglia markers, C3 and MFG‐E8, while increasing the sleeping period. A NA precursor l‐threo‐dihydroxyphenylserine abolished the reserpine‐induced changes. These results suggest that microglia may eliminate presumably weak synapses during every sleep phase. The circadian changes in concentrations of circulating glucocorticoids and brain NA might be correlated with the circadian changes of microglial phenotypes and synaptic strength.

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Section: Circadian Changes In Expression Of Synaptic and Microglialmentioning

confidence: 93%

Phagocytic elimination of synapses by microglia during sleep

Choudhury

Miyanishi

Tamano

et al. 2019

Glia

103

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“…This cluster also contains ADGRE1 (which in mouse encodes the widely used macrophage marker F4/80 antigen) and related EMR4 (ADGRE4). We recently produced a monoclonal antibody against pig ADGRE1 and demonstrated binding to Kupffer cells (Waddell et al, 2018) although as discussed below, expression was highest on alveolar macrophages.…”

Section: The Transcriptome Of the Pig Livermentioning

confidence: 99%

Functional Annotation of the Transcriptome of the Pig, Sus scrofa, Based Upon Network Analysis of an RNAseq Transcriptional Atlas

Summers

Bush

et al. 2020

Front. Genet.

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The domestic pig (Sus scrofa) is both an economically important livestock species and a model for biomedical research. Two highly contiguous pig reference genomes have recently been released. To support functional annotation of the pig genomes and comparative analysis with large human transcriptomic data sets, we aimed to create a pig gene expression atlas. To achieve this objective, we extended a previous approach developed for the chicken. We downloaded RNAseq data sets from public repositories, down-sampled to a common depth, and quantified expression against a reference transcriptome using the mRNA quantitation tool, Kallisto. We then used the network analysis tool Graphia to identify clusters of transcripts that were coexpressed across the merged data set. Consistent with the principle of guilt-by-association, we identified coexpression clusters that were highly tissue or cell-type restricted and contained transcription factors that have previously been implicated in lineage determination. Other clusters were enriched for transcripts associated with biological processes, such as the cell cycle and oxidative phosphorylation. The same approach was used to identify coexpression clusters within RNAseq data from multiple individual liver and brain samples, highlighting cell type, process, and region-specific gene expression. Evidence of conserved expression can add confidence to assignment of orthology between pig and human genes. Many transcripts currently identified as novel genes with ENSSSCG or LOC IDs were found to be coexpressed with annotated neighbouring transcripts in the same orientation, indicating they may be products of the same transcriptional unit. The metaanalytic approach to utilising public RNAseq data is extendable to include new data sets and new species and provides a framework to support the Functional Annotation of Animals Genomes (FAANG) initiative.

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“…Among 15 RNAs in the signature, several RNAs have been reported to be associated with cancer development and prognosis. For example, ADGRE1 encodes F4/80 antigen which was expressed in immune cells and used as a monocytemacrophage marker in mice (Waddell et al, 2018). KRT84 has been reported to be up-regulated in squamous cell carcinoma and involved in metabolic pathways (Koringa et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of an Immune-Related RNA Signature to Predict Survival of Patients With Head and Neck Squamous Cell Carcinoma

Dai

Xie

2019

Front. Genet.

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Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease characterized by different molecular subgroups and clinical features. Therefore, it is important to uncover reliable molecular biomarkers for distinguishing different risk patient subgroup. Here, we conducted a multi-omics analysis to examine the joint predictive power of a multi-type RNA signature in the prognosis of HNSCC patients through integration analysis of mRNA, miRNA, and lncRNA expression profiles and clinical data in a large number of HNSCC patients. A multi-type RNA signature (15SigRS) was constructed which can classify patients into the high-risk group and low-risk group with the significantly different outcome [hazard ratio (HR) = 2.718, 95% confidence interval (CI), 2.258-3.272, p < 0.001] in the discovery data set, and subsequently validated in the Cancer Genome Atlas (TCGA) testing data set (HR = 1.299, 95% CI, 1.170-1.442, p < 0.001) and another independent GSE65858 data set (HR = 1.077, 95% CI, 1.016-1.143, p = 0.013). Further multivariate Cox regression analysis and stratification analysis demonstrated the independence of predictive performance of the 15SigRS relative to conventional clinicopathological factors. Furthermore, the 15SigRS has a prior performance in prognostic prediction than other single RNA type-based signatures. Functional analysis suggested that the 15SigRS are involved in immune-or metabolism-related KEGG pathways. In summary, our study demonstrated the potential application of mixed RNA types as molecular markers for predicting the outcome of cancer patients.

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ADGRE1 (EMR1, F4/80) Is a Rapidly-Evolving Gene Expressed in Mammalian Monocyte-Macrophages

Cited by 98 publications

References 80 publications

Phagocytic elimination of synapses by microglia during sleep

Phagocytic elimination of synapses by microglia during sleep

Functional Annotation of the Transcriptome of the Pig, Sus scrofa, Based Upon Network Analysis of an RNAseq Transcriptional Atlas

Identification and Validation of an Immune-Related RNA Signature to Predict Survival of Patients With Head and Neck Squamous Cell Carcinoma

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