Amod Kulkarni, Dhananjay B. Alagundagi, Mangesh Bhide, Prakash Patil
{"title":"RNA-seq数据的荟萃分析确定干扰素诱导基因参与促进神经侵入性病原体的血脑屏障穿越","authors":"Amod Kulkarni, Dhananjay B. Alagundagi, Mangesh Bhide, Prakash Patil","doi":"10.1007/s12031-025-02400-0","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Neuroinvasive pathogens are capable of breaching the blood–brain barrier (BBB), and causing central nervous system infections. Although the response of human brain microvascular endothelial cells (hBMECs), the forefront cells of BBB has been extensively studied, the roles of astrocytes and pericytes in modulating BBB integrity during infection remain less defined.</p><h3>Aims</h3><p>The study aims for a meta-analysis of RNA-seq data to compare the transcriptional response of hBMECs alone and in co-culture with astrocytes and pericytes (BBB-spheroids) following infection with <i>Neisseria meningitidis</i> and <i>Borrelia bavariensis</i>. Subsequently, identifying the pathogen-specific gene signatures that regulates the signalling pathways associated with infection and BBB disruption. </p><h3>Methods</h3><p>Unique and shared differentially expressed genes (DEGs) of hBMECs and BBB-spheroids were identified and analysed for functional enrichment using DAVID. Protein–protein interaction networks were constructed and analysed in Cytoscape using MCODE and cytoHubba to identify infection-related hub genes.</p><h3>Results</h3><p>A large proportion of DEGs were unique to each BBB model during infection, 49% in <i>Neisseria</i> and 66% in <i>Borrelia</i> infection, whereas only 4.9% were shared. hBMECs predominantly expressed defence-related genes, whereas BBB-spheroids expressed genes linked to barrier function. Notably, IFIH1, IFIT1, IFIT3, ISG15, MX1, OAS1, and RSAD2 were identified as regulators of the BBB’s transcriptomic response to infection.</p><h3>Conclusions</h3><p>The meta-analysis highlights distinct yet complementary roles of endothelial cells and the supporting pericytes and astrocytes in BBB regulation to bacterial invasion. The identified hub genes may serve as key regulators of infection-driven inflammation and form potential diagnostic or prognostic targets.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Meta-analysis of RNA-seq Data Identifies Involvement of Interferon-Induced Genes to Facilitate Blood–Brain Barrier Traversal of Neuroinvasive Pathogens\",\"authors\":\"Amod Kulkarni, Dhananjay B. Alagundagi, Mangesh Bhide, Prakash Patil\",\"doi\":\"10.1007/s12031-025-02400-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Neuroinvasive pathogens are capable of breaching the blood–brain barrier (BBB), and causing central nervous system infections. Although the response of human brain microvascular endothelial cells (hBMECs), the forefront cells of BBB has been extensively studied, the roles of astrocytes and pericytes in modulating BBB integrity during infection remain less defined.</p><h3>Aims</h3><p>The study aims for a meta-analysis of RNA-seq data to compare the transcriptional response of hBMECs alone and in co-culture with astrocytes and pericytes (BBB-spheroids) following infection with <i>Neisseria meningitidis</i> and <i>Borrelia bavariensis</i>. Subsequently, identifying the pathogen-specific gene signatures that regulates the signalling pathways associated with infection and BBB disruption. </p><h3>Methods</h3><p>Unique and shared differentially expressed genes (DEGs) of hBMECs and BBB-spheroids were identified and analysed for functional enrichment using DAVID. Protein–protein interaction networks were constructed and analysed in Cytoscape using MCODE and cytoHubba to identify infection-related hub genes.</p><h3>Results</h3><p>A large proportion of DEGs were unique to each BBB model during infection, 49% in <i>Neisseria</i> and 66% in <i>Borrelia</i> infection, whereas only 4.9% were shared. hBMECs predominantly expressed defence-related genes, whereas BBB-spheroids expressed genes linked to barrier function. Notably, IFIH1, IFIT1, IFIT3, ISG15, MX1, OAS1, and RSAD2 were identified as regulators of the BBB’s transcriptomic response to infection.</p><h3>Conclusions</h3><p>The meta-analysis highlights distinct yet complementary roles of endothelial cells and the supporting pericytes and astrocytes in BBB regulation to bacterial invasion. 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Meta-analysis of RNA-seq Data Identifies Involvement of Interferon-Induced Genes to Facilitate Blood–Brain Barrier Traversal of Neuroinvasive Pathogens
Background
Neuroinvasive pathogens are capable of breaching the blood–brain barrier (BBB), and causing central nervous system infections. Although the response of human brain microvascular endothelial cells (hBMECs), the forefront cells of BBB has been extensively studied, the roles of astrocytes and pericytes in modulating BBB integrity during infection remain less defined.
Aims
The study aims for a meta-analysis of RNA-seq data to compare the transcriptional response of hBMECs alone and in co-culture with astrocytes and pericytes (BBB-spheroids) following infection with Neisseria meningitidis and Borrelia bavariensis. Subsequently, identifying the pathogen-specific gene signatures that regulates the signalling pathways associated with infection and BBB disruption.
Methods
Unique and shared differentially expressed genes (DEGs) of hBMECs and BBB-spheroids were identified and analysed for functional enrichment using DAVID. Protein–protein interaction networks were constructed and analysed in Cytoscape using MCODE and cytoHubba to identify infection-related hub genes.
Results
A large proportion of DEGs were unique to each BBB model during infection, 49% in Neisseria and 66% in Borrelia infection, whereas only 4.9% were shared. hBMECs predominantly expressed defence-related genes, whereas BBB-spheroids expressed genes linked to barrier function. Notably, IFIH1, IFIT1, IFIT3, ISG15, MX1, OAS1, and RSAD2 were identified as regulators of the BBB’s transcriptomic response to infection.
Conclusions
The meta-analysis highlights distinct yet complementary roles of endothelial cells and the supporting pericytes and astrocytes in BBB regulation to bacterial invasion. The identified hub genes may serve as key regulators of infection-driven inflammation and form potential diagnostic or prognostic targets.
期刊介绍：
The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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