Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology

文献类型： 外文期刊

第一作者： Fang, Chuantao

作者： Fang, Chuantao;Sun, Licheng;Lu, Yujia;Guo, Jingjing;Mei, Xinyu;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Zhang, Xiaodan;Yang, Lin;Wang, Min;Tan, Yanfeng;Zhang, Jinsen;Liu, Guoping;Zhang, Fayong;Zhao, Rui;Qi, Dashi;Fang, Chuantao;Liu, Yi;Xiao, Jianbo;Gao, Xin;Zhu, Li;Ren, Maozhi;Ma, Shaojie;Zhao, Rui;Zhao, Rui

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）

ISSN：

年卷期： 2025 年 16 卷 1 期

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收录情况： SCI

摘要： Focal cortical dysplasia type II (FCDII) is a major cause of drug-resistant epilepsy, but genetic factors explain only some cases, suggesting other mechanisms. In this study, we conduct a molecular analysis of brain lesions and adjacent areas in FCDIIb patients. By analyzing over 217,506 single-nucleus transcriptional profiles from 15 individuals, we find significant changes in smooth muscle cells (SMCs) and astrocytes. We identify abnormal vascular malformations and a unique type of SMC that we call "Firework cells", which migrate from blood vessels into the brain parenchyma and associate with VIM+ cells. These abnormalities create localized ischemic-hypoxic (I/H) microenvironments, as confirmed by clinical data, further impairing astrocyte function, activating the HIF-1 alpha/mTOR/S6 pathway, and causing neuronal loss. Using zebrafish models, we demonstrate that vascular abnormalities resulting in I/H environments promote seizures. Our results highlight vascular malformations as a factor in FCDIIb pathogenesis, suggesting potential therapeutic avenues.

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