Modeling the precise interaction of glioblastoma with human brain region-specific organoids
Summary: Glioblastoma is a highly aggressive malignant tumor of the central nervous system, but the interaction between glioblastoma and different types of neurons remains unclear. Here, we established a co-culture model in vitro using 3D printed molds with microchannels, in which glioblastoma organ...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224003328 |
| _version_ | 1797303942165561344 |
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| author | Qi Fan Hanze Wang Tianyi Gu Huihui Liu Peng Deng Bo Li Hui Yang Ying Mao Zhicheng Shao |
| author_facet | Qi Fan Hanze Wang Tianyi Gu Huihui Liu Peng Deng Bo Li Hui Yang Ying Mao Zhicheng Shao |
| author_sort | Qi Fan |
| collection | DOAJ |
| description | Summary: Glioblastoma is a highly aggressive malignant tumor of the central nervous system, but the interaction between glioblastoma and different types of neurons remains unclear. Here, we established a co-culture model in vitro using 3D printed molds with microchannels, in which glioblastoma organoids (GB), dorsal forebrain organoids (DO, mainly composed of excitatory neurons), and ventral forebrain organoids (VO, mainly composed of inhibitory neurons) were assembled. Our results indicate that DO has a greater impact on altered gene expression profiles of GB, resulting in increased invasive potential. GB cells preferentially invaded DO along axons, whereas this phenomenon was not observed in VO. Furthermore, GB cells selectively inhibited neurite outgrowth in DOs and reduced the expression of the vesicular GABA transporter (VGAT), leading to neuronal hyperexcitability. By revealing how glioblastoma interacts with brain cells, our study provides a more comprehensive understanding of this disease. |
| first_indexed | 2024-03-08T00:00:55Z |
| format | Article |
| id | doaj.art-8ebb587ac0dd4a2ea02f61d81d3b855f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T00:00:55Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8ebb587ac0dd4a2ea02f61d81d3b855f2024-02-18T04:42:40ZengElsevieriScience2589-00422024-03-01273109111Modeling the precise interaction of glioblastoma with human brain region-specific organoidsQi Fan0Hanze Wang1Tianyi Gu2Huihui Liu3Peng Deng4Bo Li5Hui Yang6Ying Mao7Zhicheng Shao8Institutes for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children’s Medical Center, Children’s Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, ChinaHuman Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai 201203, ChinaInstitutes for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children’s Medical Center, Children’s Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, ChinaDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, ChinaDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding authorDepartment of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding authorInstitutes for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children’s Medical Center, Children’s Hospital, Fudan University, Shanghai, China; Corresponding authorSummary: Glioblastoma is a highly aggressive malignant tumor of the central nervous system, but the interaction between glioblastoma and different types of neurons remains unclear. Here, we established a co-culture model in vitro using 3D printed molds with microchannels, in which glioblastoma organoids (GB), dorsal forebrain organoids (DO, mainly composed of excitatory neurons), and ventral forebrain organoids (VO, mainly composed of inhibitory neurons) were assembled. Our results indicate that DO has a greater impact on altered gene expression profiles of GB, resulting in increased invasive potential. GB cells preferentially invaded DO along axons, whereas this phenomenon was not observed in VO. Furthermore, GB cells selectively inhibited neurite outgrowth in DOs and reduced the expression of the vesicular GABA transporter (VGAT), leading to neuronal hyperexcitability. By revealing how glioblastoma interacts with brain cells, our study provides a more comprehensive understanding of this disease.http://www.sciencedirect.com/science/article/pii/S2589004224003328MicroenvironmentMolecular biologyNeuroscienceTechniques in neuroscienceOmicsTranscriptomics |
| spellingShingle | Qi Fan Hanze Wang Tianyi Gu Huihui Liu Peng Deng Bo Li Hui Yang Ying Mao Zhicheng Shao Modeling the precise interaction of glioblastoma with human brain region-specific organoids iScience Microenvironment Molecular biology Neuroscience Techniques in neuroscience Omics Transcriptomics |
| title | Modeling the precise interaction of glioblastoma with human brain region-specific organoids |
| title_full | Modeling the precise interaction of glioblastoma with human brain region-specific organoids |
| title_fullStr | Modeling the precise interaction of glioblastoma with human brain region-specific organoids |
| title_full_unstemmed | Modeling the precise interaction of glioblastoma with human brain region-specific organoids |
| title_short | Modeling the precise interaction of glioblastoma with human brain region-specific organoids |
| title_sort | modeling the precise interaction of glioblastoma with human brain region specific organoids |
| topic | Microenvironment Molecular biology Neuroscience Techniques in neuroscience Omics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224003328 |
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