Comprehensive analysis of neuronal guidance cue expression regulation during monocyte-to-macrophage differentiation reveals post-transcriptional regulation of semaphorin7A by the RNA-binding protein quaking
| Autor: | Eric P van der Veer, Oscar Rj van Hengel, Janine M van Gils, Jurrien Prins, Anton Jan van Zonneveld, Barend W. Florijn, Dianne Vreeken, Mieke F van Essen, Hilde Van Esch, Huayu Zhang, Ruben G de Bruin, J. Duijs |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
THP-1 Cells RNA-binding protein quaking Haploinsufficiency Semaphorins Research & Experimental Medicine Monocyte semaphorin Monocytes 0302 clinical medicine RNA Processing Post-Transcriptional 3' Untranslated Regions Regulation of gene expression microRNA RNA-Binding Proteins Cell Differentiation Cell biology Axon Guidance Infectious Diseases medicine.anatomical_structure Medicine Research & Experimental 030220 oncology & carcinogenesis Monocyte differentiation Female Life Sciences & Biomedicine lcsh:Immunologic diseases. Allergy Biochemistry & Molecular Biology Immunology Primary Cell Culture SEMA4D macrophage Biology Microbiology 03 medical and health sciences medicine Humans Molecular Biology Post-transcriptional regulation Science & Technology Gene Expression Profiling Macrophages Siblings Cell Biology Original Articles Protein Quaking MicroRNAs 030104 developmental biology RNA lcsh:RC581-607 |
| Zdroj: | Innate Immunity Innate Immunity, Vol 27 (2021) Innate Immunity, 27(2), 118-132. SAGE PUBLICATIONS LTD |
| Popis: | In response to inflammatory cytokines and chemokines, monocytes differentiate into macrophages. Comprehensive analysis of gene expression regulation of neuronal guidance cue (NGC) ligands and receptors in the monocyte-to-macrophage differentiation process is not available yet. We performed transcriptome profiling in both human primary PBMCs/PBMC-derived macrophages and THP-1 cells/THP-1-macrophages using microarray or RNA sequencing methods. Pathway analysis showed that the axonal guidance pathway is significantly regulated upon monocyte differentiation. We confirmed NGC ligands and receptors which were consistently regulated, including SEMA4D, SEMA7A, NRP1, NRP2, PLXNA1 and PLXNA3. The involvement of RNA-binding protein quaking (QKI) in the regulation of NGC expression was investigated using monocytes and macrophages from a QKI haplo-insufficient patient and her healthy sibling. This revealed a positive correlation of SEMA7A expression with QKI expression. In silico analysis of 3'UTRs of NGCs proposed the competitive binding of QKI to proximal microRNA targeting sites as the mechanism of QKI-dependent regulation of SEMA7A. RNA immunoprecipitation confirmed an interaction of QKI with the 3'UTR of SEMA7A. Loss of SEMA7A resulted in monocyte differentiation towards a more anti-inflammatory macrophage. Taken together, the axonal guidance pathway is regulated during monocyte-to-macrophage differentiation, and the regulation is in line with the necessary functional adaption for the specialised role of macrophages. ispartof: INNATE IMMUNITY vol:27 issue:2 pages:118-132 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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