Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia
Summary: Focal cortical dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-nuclei profiling to map the chromatin accessibility and transcriptome landscapes of...
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224025628 |
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| author | Isabella C. Galvão Manuela Lemoine Lauana A. Messias Patrícia A.O.R.A. Araújo Jaqueline C. Geraldis Clarissa L. Yasuda Marina K.M. Alvim Enrico Ghizoni Helder Tedeschi Fernando Cendes Fabio Rogerio Iscia Lopes-Cendes Diogo F.T. Veiga |
| author_facet | Isabella C. Galvão Manuela Lemoine Lauana A. Messias Patrícia A.O.R.A. Araújo Jaqueline C. Geraldis Clarissa L. Yasuda Marina K.M. Alvim Enrico Ghizoni Helder Tedeschi Fernando Cendes Fabio Rogerio Iscia Lopes-Cendes Diogo F.T. Veiga |
| author_sort | Isabella C. Galvão |
| collection | DOAJ |
| description | Summary: Focal cortical dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-nuclei profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-nuclei dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a distinct neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering directions for targeted therapy development. |
| format | Article |
| id | doaj-art-39b84b66c0d941e4936e1218d8b3b531 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-39b84b66c0d941e4936e1218d8b3b5312024-12-22T05:28:59ZengElsevieriScience2589-00422024-12-012712111337Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasiaIsabella C. Galvão0Manuela Lemoine1Lauana A. Messias2Patrícia A.O.R.A. Araújo3Jaqueline C. Geraldis4Clarissa L. Yasuda5Marina K.M. Alvim6Enrico Ghizoni7Helder Tedeschi8Fernando Cendes9Fabio Rogerio10Iscia Lopes-Cendes11Diogo F.T. Veiga12Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilThe Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, BrazilDepartment of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), São Paulo, Brazil; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, São Paulo, Brazil; Corresponding authorSummary: Focal cortical dysplasia (FCD) is a neurodevelopmental condition characterized by malformations of the cerebral cortex that often cause drug-resistant epilepsy. In this study, we performed multi-omics single-nuclei profiling to map the chromatin accessibility and transcriptome landscapes of FCD type II, generating a comprehensive multimodal single-nuclei dataset comprising 61,525 cells from 11 clinical samples of lesions and controls. Our findings revealed profound chromatin, transcriptomic, and cellular alterations affecting neuronal and glial cells in FCD lesions, including the selective loss of upper-layer excitatory neurons, significant expansion of oligodendrocytes and immature astrocytic populations, and a distinct neuronal subpopulation harboring dysmorphic neurons. Furthermore, we uncovered activated microglia subsets, particularly in FCD IIb cases. This comprehensive study unveils neuronal and glial cell states driving FCD development and epileptogenicity, enhancing our understanding of FCD and offering directions for targeted therapy development.http://www.sciencedirect.com/science/article/pii/S2589004224025628Biological sciencesNeuroscienceDevelopmental neuroscienceOmics |
| spellingShingle | Isabella C. Galvão Manuela Lemoine Lauana A. Messias Patrícia A.O.R.A. Araújo Jaqueline C. Geraldis Clarissa L. Yasuda Marina K.M. Alvim Enrico Ghizoni Helder Tedeschi Fernando Cendes Fabio Rogerio Iscia Lopes-Cendes Diogo F.T. Veiga Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia iScience Biological sciences Neuroscience Developmental neuroscience Omics |
| title | Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| title_full | Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| title_fullStr | Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| title_full_unstemmed | Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| title_short | Multimodal single-cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| title_sort | multimodal single cell profiling reveals neuronal vulnerability and pathological cell states in focal cortical dysplasia |
| topic | Biological sciences Neuroscience Developmental neuroscience Omics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224025628 |
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