Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain

Background: Discoidin domain receptor tyrosine kinase 1 (DDR1) is present in multiple types of epithelial cells and is highly expressed in the nervous system. Previous studies have revealed that DDR1 is involved in schizophrenia (SCZ). Although the expression of DDR1 in oligodendrocytes has been des...

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Autores: Muntané, Gerard, Chillida, Marc, Aranda, Selena, Navarro i Cuartiellas, Arcadi, 1969-, Vilella, Elisabet
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/48592
Acesso em linha:http://hdl.handle.net/10230/48592
http://dx.doi.org/10.1002/brb3.2309
Access Level:acceso abierto
Palavra-chave:DDR1
Astrocytes
Coexpression
Human brain
Microglia type 2
Oligodendrocytes
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spelling Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brainMuntané, GerardChillida, MarcAranda, SelenaNavarro i Cuartiellas, Arcadi, 1969-Vilella, ElisabetDDR1AstrocytesCoexpressionHuman brainMicroglia type 2OligodendrocytesBackground: Discoidin domain receptor tyrosine kinase 1 (DDR1) is present in multiple types of epithelial cells and is highly expressed in the nervous system. Previous studies have revealed that DDR1 is involved in schizophrenia (SCZ). Although the expression of DDR1 in oligodendrocytes has been described, its role in brain myelination is not well understood. In this study, we aimed to explore the coexpression network of DDR1 in the human brain and to compare the list of DDR1 coexpressing genes with the list of genes containing single nucleotide polymorphisms (SNPs) that are associated with SCZ. Materials and methods: We used a weighted gene coexpression network analysis (WGCNA) of a dataset from four brain areas (the dorsolateral prefrontal cortex, primary motor cortex, hippocampus, and striatum) and from four different intervals (I) of life (I-1 = 10-38 weeks postconception, I-2 ≥0 to < 6 years, I-3 ≥ 6 to < 40 years, and I-4 ≥ 40 years of age). We compared the list of genes that are associated with SCZ in the GWAS Catalog with the list of genes coexpressing with DDR1 in each interval. Results: Our study revealed that DDR1 was coexpressed with oligodendrocyte-related genes mainly in I-2 (adjP = 5.66e-24) and I-3 (adjP = 2.8e-114), which coincided with the coexpression of DDR1 with myelination-related genes (adjP = 9.04e-03 and 2.51e-08, respectively). DDR1 was also coexpressed with astrocyte-related genes in I-1 (adjP = 1.11e-71), I-2 (adjP = 2.12e-20) and I-4 (adjP = 9.93e-52) and with type 2 microglia-related genes in I-1 (adjP = 2.84e-08), I-2 (adjP = 5.68e-16) and I-4 (adjP = 3.66e-10). Moreover, we observed significant enrichment of SCZ susceptibility genes within the coexpression modules containing DDR1 in I-1 and I-4 (P = 1e-04 and 0.0037, respectively), during which the DDR1 module showed the highest association with the astrocytes. Conclusions: Our study confirmed that DDR1 is coexpressed with oligodendrocyte- and myelin-related genes in the human brain but suggests that DDR1 may contribute mainly to SCZ risk through its role in other glial cell types, such as astrocytes.Wiley202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/48592http://dx.doi.org/10.1002/brb3.2309reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésBrain Behav. 2021;11(8):e2309© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/485922026-06-12T07:21:37Z
dc.title.none.fl_str_mv Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
title Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
spellingShingle Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
Muntané, Gerard
DDR1
Astrocytes
Coexpression
Human brain
Microglia type 2
Oligodendrocytes
title_short Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
title_full Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
title_fullStr Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
title_full_unstemmed Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
title_sort Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain
dc.creator.none.fl_str_mv Muntané, Gerard
Chillida, Marc
Aranda, Selena
Navarro i Cuartiellas, Arcadi, 1969-
Vilella, Elisabet
author Muntané, Gerard
author_facet Muntané, Gerard
Chillida, Marc
Aranda, Selena
Navarro i Cuartiellas, Arcadi, 1969-
Vilella, Elisabet
author_role author
author2 Chillida, Marc
Aranda, Selena
Navarro i Cuartiellas, Arcadi, 1969-
Vilella, Elisabet
author2_role author
author
author
author
dc.subject.none.fl_str_mv DDR1
Astrocytes
Coexpression
Human brain
Microglia type 2
Oligodendrocytes
topic DDR1
Astrocytes
Coexpression
Human brain
Microglia type 2
Oligodendrocytes
description Background: Discoidin domain receptor tyrosine kinase 1 (DDR1) is present in multiple types of epithelial cells and is highly expressed in the nervous system. Previous studies have revealed that DDR1 is involved in schizophrenia (SCZ). Although the expression of DDR1 in oligodendrocytes has been described, its role in brain myelination is not well understood. In this study, we aimed to explore the coexpression network of DDR1 in the human brain and to compare the list of DDR1 coexpressing genes with the list of genes containing single nucleotide polymorphisms (SNPs) that are associated with SCZ. Materials and methods: We used a weighted gene coexpression network analysis (WGCNA) of a dataset from four brain areas (the dorsolateral prefrontal cortex, primary motor cortex, hippocampus, and striatum) and from four different intervals (I) of life (I-1 = 10-38 weeks postconception, I-2 ≥0 to < 6 years, I-3 ≥ 6 to < 40 years, and I-4 ≥ 40 years of age). We compared the list of genes that are associated with SCZ in the GWAS Catalog with the list of genes coexpressing with DDR1 in each interval. Results: Our study revealed that DDR1 was coexpressed with oligodendrocyte-related genes mainly in I-2 (adjP = 5.66e-24) and I-3 (adjP = 2.8e-114), which coincided with the coexpression of DDR1 with myelination-related genes (adjP = 9.04e-03 and 2.51e-08, respectively). DDR1 was also coexpressed with astrocyte-related genes in I-1 (adjP = 1.11e-71), I-2 (adjP = 2.12e-20) and I-4 (adjP = 9.93e-52) and with type 2 microglia-related genes in I-1 (adjP = 2.84e-08), I-2 (adjP = 5.68e-16) and I-4 (adjP = 3.66e-10). Moreover, we observed significant enrichment of SCZ susceptibility genes within the coexpression modules containing DDR1 in I-1 and I-4 (P = 1e-04 and 0.0037, respectively), during which the DDR1 module showed the highest association with the astrocytes. Conclusions: Our study confirmed that DDR1 is coexpressed with oligodendrocyte- and myelin-related genes in the human brain but suggests that DDR1 may contribute mainly to SCZ risk through its role in other glial cell types, such as astrocytes.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
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/10230/48592
http://dx.doi.org/10.1002/brb3.2309
url http://hdl.handle.net/10230/48592
http://dx.doi.org/10.1002/brb3.2309
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Brain Behav. 2021;11(8):e2309
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 Wiley
publisher.none.fl_str_mv Wiley
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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