Articles producció científica> Medicina i Cirurgia

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

  • Dades identificatives

    Identificador: imarina:9226231
    Autors:
    Muntane, GerardChillida, MarcAranda, SelenaNavarro, ArcadiVilella, Elisabet
    Resum:
    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), durin
  • Altres:

    Autor segons l'article: Muntane, Gerard; Chillida, Marc; Aranda, Selena; Navarro, Arcadi; Vilella, Elisabet;
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Aranda Castel, Selena / Muntané Medina, Gerard / Vilella Cuadrada, Elisabet
    Paraules clau: White-matter Weighted gene coexpression network analysis Transcriptome Sox10 gene Slc2a5 gene Schizophrenia risk gene Schizophrenia Receptor protein-tyrosine kinases Protein tyrosine kinase Plp1 gene Pdgfra gene Overlapping gene Oligodendroglia Oligodendrocytes Oligodendrocyte related gene Olig2 gene Olig1 gene Neurons Myelination Myelin Microglia type 2 Microglia Microarray analysis Mbp gene Mag gene Humans Human brain Human Genome-wide association study Genetics Gene ontology Gene expression Gene coexpression Gene Gac gene Expression Disorders Discoidin domain receptor 1 Ddr1 Database Cxc3l1 gene Cspg4 gene Col4a1 gene Col1a1 gene Coexpression Cnp gene Cldn11 gene Cd53 gene Brain development Brain Astrocytes Astrocyte Article Analysis
    Resum: 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.
    Àrees temàtiques: Neurosciences Medicina ii Medicina i Interdisciplinar Farmacia Engenharias iv Ciências biológicas ii Ciências biológicas i Biotecnología Behavioral sciences Behavioral neuroscience
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    Adreça de correu electrònic de l'autor: gerard.muntane@urv.cat elisabet.vilella@urv.cat selena.aranda@estudiants.urv.cat
    Identificador de l'autor: 0000-0002-1887-5919
    Data d'alta del registre: 2024-07-27
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Brain And Behavior. 11 (8):
    Referència de l'ítem segons les normes APA: Muntane, Gerard; Chillida, Marc; Aranda, Selena; Navarro, Arcadi; Vilella, Elisabet; (2021). Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain. Brain And Behavior, 11(8), -. DOI: 10.1002/brb3.2309
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2021
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Behavioral Neuroscience,Behavioral Sciences,Neurosciences
    White-matter
    Weighted gene coexpression network analysis
    Transcriptome
    Sox10 gene
    Slc2a5 gene
    Schizophrenia risk gene
    Schizophrenia
    Receptor protein-tyrosine kinases
    Protein tyrosine kinase
    Plp1 gene
    Pdgfra gene
    Overlapping gene
    Oligodendroglia
    Oligodendrocytes
    Oligodendrocyte related gene
    Olig2 gene
    Olig1 gene
    Neurons
    Myelination
    Myelin
    Microglia type 2
    Microglia
    Microarray analysis
    Mbp gene
    Mag gene
    Humans
    Human brain
    Human
    Genome-wide association study
    Genetics
    Gene ontology
    Gene expression
    Gene coexpression
    Gene
    Gac gene
    Expression
    Disorders
    Discoidin domain receptor 1
    Ddr1
    Database
    Cxc3l1 gene
    Cspg4 gene
    Col4a1 gene
    Col1a1 gene
    Coexpression
    Cnp gene
    Cldn11 gene
    Cd53 gene
    Brain development
    Brain
    Astrocytes
    Astrocyte
    Article
    Analysis
    Neurosciences
    Medicina ii
    Medicina i
    Interdisciplinar
    Farmacia
    Engenharias iv
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Behavioral sciences
    Behavioral neuroscience
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