학술논문
Single-cell transcriptomics and surface epitope detection in human brain epileptic lesions identifies pro-inflammatory signaling
Document Type
Article
Author
Kumar, Pavanish; Lim, Amanda; Hazirah, Sharifah Nur; Chua, Camillus Jian Hui; Ngoh, Adeline; Poh, Su Li; Yeo, Tong Hong; Lim, Jocelyn; Ling, Simon; Sutamam, Nursyuhadah Binte; Petretto, Enrico; Low, David Chyi Yeu; Zeng, Li; Tan, Eng-King; Arkachaisri, Thaschawee; Yeo, Joo Guan; Ginhoux, Florent; Chan, Derrick; Albani, Salvatore
Source
Nature Neuroscience; July 2022, Vol. 25 Issue: 7 p956-966, 11p
Subject
Language
ISSN
10976256; 15461726
Abstract
Epileptogenic triggers are multifactorial and not well understood. Here we aimed to address the hypothesis that inappropriate pro-inflammatory mechanisms contribute to the pathogenesis of refractory epilepsy (non-responsiveness to antiepileptic drugs) in human patients. We used single-cell cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to reveal the immunotranscriptome of surgically resected epileptic lesion tissues. Our approach uncovered a pro-inflammatory microenvironment, including extensive activation of microglia and infiltration of other pro-inflammatory immune cells. These findings were supported by ligand–receptor (LR) interactome analysis, which demonstrated potential mechanisms of infiltration and evidence of direct physical interactions between microglia and T cells. Together, these data provide insight into the immune microenvironment in epileptic tissue, which may aid the development of new therapeutics.