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

Author(s):Show less -

Galvao, Isabella C. ; Kandratavicius, Ludmyla ; Messias, Lauana A. ; Athie, Maria C. P. ; Assis-Mendonca, Guilherme R. ; Alvim, Marina K. M. ; Ghizoni, Enrico ; Tedeschi, Helder ; Yasuda, Clarissa L. ; Cendes, Fernando ; Vieira, Andre S. ; Rogerio, Fabio ; Lopes-Cendes, Iscia ; Veiga, Diogo F. T.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 13, n. 1, p. 10-pg., 2023-08-16.

Abstract

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. (AU)

• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/04780-4 - Unraveling the molecular mechanisms underlying parasite-host interaction in Taenia solium Neurocysticercosis
• Grantee: Maria Carolina Pedro Athié
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/08259-0 - Analysis of the transcriptome of brain tissue from epilepsy patients with focal cortical dysplasia or mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)
• Grantee: Fábio Rogério
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/15112-2 - Multi-omics integration for detection of novel chromatin biomarkers in human disorders: towards a better understanding of disease mechanisms and novel therapies
• Grantee: Diogo Fernando Troggian Veiga
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 22/01530-2 - Integrative analysis of single-cell epigenomes and transcriptomes to reveal novel biomarkers in Epilepsy
• Grantee: Isabella Cotta Galvão
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/07382-2 - Multi-omics integration for detection of novel chromatin biomarkers in human disorders: towards a better understanding of disease mechanisms and novel therapies
• Grantee: Diogo Fernando Troggian Veiga
• Support Opportunities: Research Grants - Young Investigators Grants