Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis
Abstract Background Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-024-05051-8 |
| _version_ | 1797266661431050240 |
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| author | Wenshuang Wang Yanhong Ji Zhexu Dong Zheran Liu Shuang Chen Lei Dai Xiaolan Su Qingyuan Jiang Hongxin Deng |
| author_facet | Wenshuang Wang Yanhong Ji Zhexu Dong Zheran Liu Shuang Chen Lei Dai Xiaolan Su Qingyuan Jiang Hongxin Deng |
| author_sort | Wenshuang Wang |
| collection | DOAJ |
| description | Abstract Background Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. Methods Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. Results Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. Conclusions Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics. |
| first_indexed | 2024-04-25T01:04:14Z |
| format | Article |
| id | doaj.art-c9fbe556209f490d9b8874959c145d19 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-25T01:04:14Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-c9fbe556209f490d9b8874959c145d192024-03-10T12:21:06ZengBMCJournal of Translational Medicine1479-58762024-03-0122112410.1186/s12967-024-05051-8Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysisWenshuang Wang0Yanhong Ji1Zhexu Dong2Zheran Liu3Shuang Chen4Lei Dai5Xiaolan Su6Qingyuan Jiang7Hongxin Deng8Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Obstetrics, Sichuan Provincial Hospital for Women and ChildrenDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract Background Neural Tube Defects (NTDs) are congenital malformations of the central nervous system resulting from the incomplete closure of the neural tube during early embryonic development. Neuroinflammation refers to the inflammatory response in the nervous system, typically resulting from damage to neural tissue. Immune-related processes have been identified in NTDs, however, the detailed relationship and underlying mechanisms between neuroinflammation and NTDs remain largely unclear. In this study, we utilized integrated multi-omics analysis to explore the role of neuroinflammation in NTDs and identify potential prenatal diagnostic markers using a murine model. Methods Nine public datasets from Gene Expression Omnibus (GEO) and ArrayExpress were mined using integrated multi-omics analysis to characterize the molecular landscape associated with neuroinflammation in NTDs. Special attention was given to the involvement of macrophages in neuroinflammation within amniotic fluid, as well as the dynamics of macrophage polarization and their interactions with neural cells at single-cell resolution. We also used qPCR assay to validate the key TFs and candidate prenatal diagnostic genes identified through the integrated analysis in a retinoic acid-induced NTDs mouse model. Results Our analysis indicated that neuroinflammation is a critical pathological feature of NTDs, regulated both transcriptionally and epigenetically within central nervous system tissues. Key alterations in gene expression and pathways highlighted the crucial role of STATs molecules in the JAK-STAT signaling pathway in regulating NTDs-associated neuroinflammation. Furthermore, single-cell resolution analysis revealed significant polarization of macrophages and their interaction with neural cells in amniotic fluid, underscoring their central role in mediating neuroinflammation associated with NTDs. Finally, we identified a set of six potential prenatal diagnostic genes, including FABP7, CRMP1, SCG3, SLC16A10, RNASE6 and RNASE1, which were subsequently validated in a murine NTDs model, indicating their promise as prospective markers for prenatal diagnosis of NTDs. Conclusions Our study emphasizes the pivotal role of neuroinflammation in the progression of NTDs and underlines the potential of specific inflammatory and neural markers as novel prenatal diagnostic tools. These findings provide important clues for further understanding the underlying mechanisms between neuroinflammation and NTDs, and offer valuable insights for the future development of prenatal diagnostics.https://doi.org/10.1186/s12967-024-05051-8Neural tube defects (NTDs)Multi-omics analysisNeuroinflammationJAK-STAT signaling pathwayMacrophage polarizationPrenatal diagnosis |
| spellingShingle | Wenshuang Wang Yanhong Ji Zhexu Dong Zheran Liu Shuang Chen Lei Dai Xiaolan Su Qingyuan Jiang Hongxin Deng Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis Journal of Translational Medicine Neural tube defects (NTDs) Multi-omics analysis Neuroinflammation JAK-STAT signaling pathway Macrophage polarization Prenatal diagnosis |
| title | Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis |
| title_full | Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis |
| title_fullStr | Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis |
| title_full_unstemmed | Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis |
| title_short | Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis |
| title_sort | characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi omics analysis |
| topic | Neural tube defects (NTDs) Multi-omics analysis Neuroinflammation JAK-STAT signaling pathway Macrophage polarization Prenatal diagnosis |
| url | https://doi.org/10.1186/s12967-024-05051-8 |
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