Identifying cellular markers of focal cortical dysplasia type II with cell-type deconvolution and single-cell signatures.

Autor: Galvão IC; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Kandratavicius L; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Messias LA; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Athié MCP; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Assis-Mendonça GR; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Alvim MKM; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Ghizoni E; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Tedeschi H; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Yasuda CL; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Cendes F; Department of Neurology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Vieira AS; Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Rogerio F; Department of Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Lopes-Cendes I; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil., Veiga DFT; Department of Translational Medicine, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil. dfveiga@unicamp.br.; The Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Brazil. dfveiga@unicamp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Aug 16; Vol. 13 (1), pp. 13321. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1038/s41598-023-40240-3
Abstrakt: Focal cortical dysplasia (FCD) is a brain malformation that causes medically refractory epilepsy. FCD is classified into three categories based on structural and cellular abnormalities, with FCD type II being the most common and characterized by disrupted organization of the cortex and abnormal neuronal development. In this study, we employed cell-type deconvolution and single-cell signatures to analyze bulk RNA-seq from multiple transcriptomic studies, aiming to characterize the cellular composition of brain lesions in patients with FCD IIa and IIb subtypes. Our deconvolution analyses revealed specific cellular changes in FCD IIb, including neuronal loss and an increase in reactive astrocytes (astrogliosis) when compared to FCD IIa. Astrogliosis in FCD IIb was further supported by a gene signature analysis and histologically confirmed by glial fibrillary acidic protein (GFAP) immunostaining. Overall, our findings demonstrate that FCD II subtypes exhibit differential neuronal and glial compositions, with astrogliosis emerging as a hallmark of FCD IIb. These observations, validated in independent patient cohorts and confirmed using immunohistochemistry, offer novel insights into the involvement of glial cells in FCD type II pathophysiology and may contribute to the development of targeted therapies for this condition.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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