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
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 transcrip...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2021-02-01
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| Series: | Innate Immunity |
| Online Access: | https://doi.org/10.1177/1753425920966645 |
| _version_ | 1818446723939303424 |
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| author | Huayu Zhang Jurriën Prins Dianne Vreeken Barend W Florijn Ruben G de Bruin Oscar RJ van Hengel Mieke F van Essen Jacques MGJ Duijs Hilde Van Esch Eric P van der Veer Anton Jan van Zonneveld Janine M van Gils |
| author_facet | Huayu Zhang Jurriën Prins Dianne Vreeken Barend W Florijn Ruben G de Bruin Oscar RJ van Hengel Mieke F van Essen Jacques MGJ Duijs Hilde Van Esch Eric P van der Veer Anton Jan van Zonneveld Janine M van Gils |
| author_sort | Huayu Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T19:52:16Z |
| format | Article |
| id | doaj.art-cbb8dffc31294d6993f3522eca85b8a1 |
| institution | Directory Open Access Journal |
| issn | 1753-4259 1753-4267 |
| language | English |
| last_indexed | 2024-12-14T19:52:16Z |
| publishDate | 2021-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Innate Immunity |
| spelling | doaj.art-cbb8dffc31294d6993f3522eca85b8a12022-12-21T22:49:23ZengSAGE PublishingInnate Immunity1753-42591753-42672021-02-012710.1177/1753425920966645Comprehensive analysis of neuronal guidance cue expression regulation during monocyte-to-macrophage differentiation reveals post-transcriptional regulation of semaphorin7A by the RNA-binding protein quakingHuayu ZhangJurriën PrinsDianne VreekenBarend W FlorijnRuben G de BruinOscar RJ van HengelMieke F van EssenJacques MGJ DuijsHilde Van EschEric P van der VeerAnton Jan van ZonneveldJanine M van GilsIn 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.https://doi.org/10.1177/1753425920966645 |
| spellingShingle | Huayu Zhang Jurriën Prins Dianne Vreeken Barend W Florijn Ruben G de Bruin Oscar RJ van Hengel Mieke F van Essen Jacques MGJ Duijs Hilde Van Esch Eric P van der Veer Anton Jan van Zonneveld Janine M van Gils 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 Innate Immunity |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1177/1753425920966645 |
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