Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data

Demyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia-OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the dem...

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Autores: Enrich-Bengoa, Jennifer, Manich, Gemma, Dégano, Irene R., Perálvarez Marín, Alex
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/56447
Acesso em linha:http://hdl.handle.net/10230/56447
http://dx.doi.org/10.3390/ijms232314868
Access Level:acceso abierto
Palavra-chave:Corpus callosum
Cuprizone
Demyelination
Microglia
Oligodendrocytes
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spelling Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic dataEnrich-Bengoa, JenniferManich, GemmaDégano, Irene R.Perálvarez Marín, AlexCorpus callosumCuprizoneDemyelinationMicrogliaOligodendrocytesDemyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia-OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the demyelination-remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia-OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.This research was funded by Spanish Government MCIN/AEI/10.13039/501100011033 (Project BFU2017-87843-R- and Project PID2020-120222GB-I00 to A.P.-M.) and by the Carlos III Health Institute and the European Regional Development Fund (CIBERCV CB16/11/00229 and FIS PI21/00163 to I.R.D.), and by the Marató TV3 Foundation (202119-33 to I.R.D.).MDPI202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/56447http://dx.doi.org/10.3390/ijms232314868reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésInt J Mol Sci. 2022 Nov 28;23(23):14868info:eu-repo/grantAgreement/ES/2PE/BFU2017-87843-Rinfo:eu-repo/grantAgreement/ES/2PE/PID2020-120222GB-I00© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/564472026-06-12T07:21:37Z
dc.title.none.fl_str_mv Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
title Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
spellingShingle Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
Enrich-Bengoa, Jennifer
Corpus callosum
Cuprizone
Demyelination
Microglia
Oligodendrocytes
title_short Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
title_full Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
title_fullStr Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
title_full_unstemmed Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
title_sort Deciphering the genetic crosstalk between microglia and oligodendrocyte precursor cells during demyelination and remyelination using transcriptomic data
dc.creator.none.fl_str_mv Enrich-Bengoa, Jennifer
Manich, Gemma
Dégano, Irene R.
Perálvarez Marín, Alex
author Enrich-Bengoa, Jennifer
author_facet Enrich-Bengoa, Jennifer
Manich, Gemma
Dégano, Irene R.
Perálvarez Marín, Alex
author_role author
author2 Manich, Gemma
Dégano, Irene R.
Perálvarez Marín, Alex
author2_role author
author
author
dc.subject.none.fl_str_mv Corpus callosum
Cuprizone
Demyelination
Microglia
Oligodendrocytes
topic Corpus callosum
Cuprizone
Demyelination
Microglia
Oligodendrocytes
description Demyelinating disorders show impaired remyelination due to failure in the differentiation of oligodendrocyte progenitor cells (OPCs) into mature myelin-forming oligodendrocytes, a process driven by microglia-OPC crosstalk. Through conducting a transcriptomic analysis of microarray studies on the demyelination-remyelination cuprizone model and using human samples of multiple sclerosis (MS), we identified molecules involved in this crosstalk. Differentially expressed genes (DEGs) of specific regions/cell types were detected in GEO transcriptomic raw data after cuprizone treatment and in MS samples, followed by functional analysis with GO terms and WikiPathways. Additionally, microglia-OPC crosstalk between microglia ligands, OPC receptors and target genes was examined with the NicheNet model. We identified 108 and 166 DEGs in the demyelinated corpus callosum (CC) at 2 and 4 weeks of cuprizone treatment; 427 and 355 DEGs in the remyelinated (4 weeks of cuprizone treatment + 14 days of normal diet) compared to 2- and 4-week demyelinated CC; 252 DEGs in MS samples and 2730 and 12 DEGs in OPC and microglia of 4-week demyelinated CC. At this time point, we found 95 common DEGs in the CC and OPCs, and one common DEG in microglia and OPCs, mostly associated with myelin and lipid metabolism. Crosstalk analysis identified 47 microglia ligands, 43 OPC receptors and 115 OPC target genes, all differentially expressed in cuprizone-treated samples and associated with myelination. Our differential expression pipeline identified demyelination/remyelination transcriptomic biomarkers in studies using diverse platforms and cell types/tissues. Cellular crosstalk analysis yielded novel markers of microglia ligands, OPC receptors and target genes.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/56447
http://dx.doi.org/10.3390/ijms232314868
url http://hdl.handle.net/10230/56447
http://dx.doi.org/10.3390/ijms232314868
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Int J Mol Sci. 2022 Nov 28;23(23):14868
info:eu-repo/grantAgreement/ES/2PE/BFU2017-87843-R
info:eu-repo/grantAgreement/ES/2PE/PID2020-120222GB-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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