Vexin is upregulated in cerebral cortical neurons by brain‐derived neurotrophic factor

Koshimizu, Hisatsugu; Suzuki, Shingo; Kawai, Anna; Miura, Ryuichiro; Ohta, Ken; Miki, Takanori; Adachi, Naoki; Matsuoka, Hiroaki

doi:10.1002/npr2.12119

Cited by 4 publications

(3 citation statements)

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“…At DIV6, BDNF was applied with a final concentration of 10 ng/mL 22 . Cells were lysed in RLT butter (RNeasy mini kit, Qiagen) for NGS library preparation at DIV 8, after 48 hours of BDNF incubation 23–25 . Striatal cells at DIV6 were fixed with 4% paraformaldehyde for immunostaining.…”

Section: Methodsmentioning

confidence: 99%

Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics

Koshimizu

Matsuoka

Nakajima

et al. 2021

Neuropsychopharm Rep

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Aim The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain‐derived neurotrophic factor (BDNF) plays multiple roles in the central nervous system, and striatal BDNF has been suggested to be involved in psychiatric and neurodegenerative disorders. However, the transcriptomic impact of BDNF on the striatum remains largely unknown. In the present study, we performed transcriptomic profiling of striatal cells stimulated with BDNF to identify enriched gene sets (GSs) and their novel target genes in vitro. Methods We carried out RNA sequencing (RNA‐Seq) of messenger RNA extracted from primary dissociated cultures of rat striatum stimulated with BDNF and conducted Generally Applicable Gene‐set Enrichment (GAGE) analysis on 10599 genes. Significant differentially expressed genes (DEGs) were determined by differential expression analysis for sequence count data 2 (DESeq2). Results GAGE analysis identified significantly enriched GSs that included GSs related to regulation and dysregulation of synaptic functions, such as synaptic vesicle cycle and addiction to nicotine and morphine, respectively. It also detected GSs related to various types of synapses, including not only GABAergic and cholinergic synapses but also dopaminergic and glutamatergic synapses. DESeq2 revealed 72 significant DEGs, among which the highest significance was observed in the apolipoprotein L domain containing 1 (Apold1). Conclusions The present study indicates that BDNF predominantly regulates the expression of synaptic‐function‐related genes and that BDNF promotes synaptogenesis in various subtypes of neurons in the developing striatum. Apold1 may represent a unique target gene of BDNF in the striatum.

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Section: Methodsmentioning

confidence: 99%

Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics

Koshimizu

Matsuoka

Nakajima

et al. 2021

Neuropsychopharm Rep

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“…S3b). Previously undescribed enriched mRNAs included Nell2 89,90 , which is involved in neuronal polarization and axon growth, Ankrd46, associated with membrane interactions, and the uncharacterized Vnx 91,92 (Fig. 3d, Extended Data Fig.…”

Section: Enriched Mrnas and Proteins In S Oriensmentioning

confidence: 99%

The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling

Kaulich,

Waselenchuk,

Fürst

et al. 2024

Preprint

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The molecular diversity of neurons and their synapses underlies the different responses and plasticity profiles that drive all neural circuits and behavior. While the extent of this diversity has been partially revealed by transcriptomic and proteomic profiling, combined studies of neuronal transcripts and proteins are limited. Here, we used microdissection of mouse hippocampal subregions and CA1 strata and fluorescence-activated synaptosome sorting (FASS) to characterize the transcripts and proteins from different hippocampal neurons and their compartments with synaptic resolution. Parallel RNA-seq and LC-MS/MS of microdissections identified over 15,000 mRNA transcripts and 10,000 proteins, revealing thousands with local enrichment such as classes of glutamate receptors and voltage-gated potassium channels, myelin-associated molecules, and adhesion molecules. Synaptosome analysis further identified specific enrichment of molecules from collagen, ribosome, solute carrier, and receptor families at different synapses formed along CA1 neurons. By integrating mRNA and protein data, we defined clusters of co-regulated molecules such as adhesion and neurofilament proteins and transporter mRNAs, and found subsets of mRNA-protein pairs with strong correlation and anti-correlation in their abundance variation. Our findings comprise a rich resource on the molecular landscape of the hippocampus and its synapses that is accessible atsyndive.org, and highlight the coordinated organization of transcripts and proteins between regions, neuronal compartments, and synapses.

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“…Our study found that it may be one of the characteristic biomarkers of PA, and further research is needed to explore its role in tumor development and its relationship with TME.Chromosome 8 open reading frame 46 (C8orf46), a human protein-coding gene, has been named Vexin. Previous studies have suggested that Vexin is involved in embryonic neurogenesis and is related to cancer progression, but its function has not yet been elucidated clearly(Koshimizu et al 2020, Moore et al 2018). Our study is the rst to report that this gene is associated with PA, which provides a new direction for future research.…”

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confidence: 99%

Clinical and Epidemiological Study of Intracranial Tumors in Children and Identification of Diagnostic Biomarkers for the Most Common Tumor Subtype and Their Relationship With the Immune Microenvironment Through Bioinformatics Analysis

Wang

Jia

et al. 2022

Preprint

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Background: Brain tumors are the second most common pediatric malignancy and have poor prognosis. Understanding the pathogenesis of tumors at the molecular level is essential for clinical treatment. We conducted a retrospective study on the epidemiology of brain tumors in children based on clinical data obtained from a neurosurgical center. After identifying the most prevalent tumor subtype, we identified new potential diagnostic biomarkers through bioinformatics analysis of the public database. Methods: All children (0–15 years) with brain tumors diagnosed histopathologically between 2010 and 2020 at the Department of Neurosurgery, Xijing Hospital, were reviewed retrospectively for age distribution, sex predilection, native location, tumor location, symptoms, and histological grade, and identified the most common tumor subtypes. Two datasets (GSE44971 and GSE44684) were downloaded from the Gene Expression Omnibus database, whereas the GSE44971 dataset was used to screen the differentially expressed genes between normal and tumor samples. Gene Ontology, Disease Ontology, and Gene Set Enrichment Analysis enrichment analyses were performed to investigate the underlying mechanisms of differentially expressed genes in the tumor. Combined with methylation data in the GSE44684 dataset, we further analyzed the correlation between methylation and gene expression levels. Two algorithms, LASSO and SVM-RFE, were used to select the hub genes of the tumor. The diagnostic value of the hub genes was assessed using the receiver operating characteristic (ROC) curve. Finally, we further evaluated the relationship between the hub gene and the tumor microenvironment and immune gene sets. Results: Overall, 650 children from 18 provinces in China were included in this study. The male-to-female ratio was 1.41:1, and the number of patients reached a peak in the 10-15-year-old group (41.4%).The most common symptoms we encountered in our institute were headache and dizziness 250 (28.2%), and nausea and vomiting 228 (25.7%). The predominant location is supratentorial, with a supratentorial to infratentorial ratio of 1.74:1. Low-grade tumors (WHO I/II) constituted 60.9% of all cases and were predominant in every age group. According to basic classification, the most common tumor subtype is pilocytic astrocytoma (PA). A total of 3264 differentially expressed genes were identified in the GSE44971 dataset, which are mainly involved in the process of neural signal transduction, immunity, and some diseases. Correlation analysis indicated that the expression of 45 differentially expressed genes was negatively correlated with promoter DNA methylation. Next, we acquired five hub genes (NCKAP1L, GPR37L1, CSPG4, PPFIA4, and C8orf46) from the 45 differentially expressed genes by intersecting the LASSO and SVM-RFE models. The ROC analysis revealed that the five hub genes had good diagnostic value for patients with PA (AUC > 0.99). Furthermore, the expression of NCKAP1L was negatively correlated with immune, stromal, and estimated scores, and positively correlated with immune gene sets.Conclusions: This study, based on the data analysis of intracranial tumors in children in a single center over the past 10 years, reflected the clinical and epidemiological characteristics of intracranial tumors in children in Northwest China to a certain extent. PA is considered the most common subtype of intracranial tumors in children. Through bioinformatics analysis, we suggested that NCKAP1L, GPR37L1, CSPG4, PPFIA4, and C8orf46 are potential biomarkers for the diagnosis of PA.

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Vexin is upregulated in cerebral cortical neurons by brain‐derived neurotrophic factor

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 4 publications

References 14 publications

Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics

Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics

The molecular diversity of hippocampal regions and strata at synaptic resolution revealed by integrated transcriptomic and proteomic profiling

Clinical and Epidemiological Study of Intracranial Tumors in Children and Identification of Diagnostic Biomarkers for the Most Common Tumor Subtype and Their Relationship With the Immune Microenvironment Through Bioinformatics Analysis

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