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Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology

Author

Listed:
  • Chuantao Fang

    (Tongji University
    Fudan University
    Tongji University School of Medicine)

  • Xiaodan Zhang

    (Fudan University)

  • Lin Yang

    (Fudan University)

  • Licheng Sun

    (Tongji University)

  • Yujia Lu

    (Tongji University)

  • Yi Liu

    (Instituto de Agroecoloxía e Alimentación (IAA) – CITEXVI)

  • Jingjing Guo

    (Tongji University)

  • Min Wang

    (Fudan University)

  • Yanfeng Tan

    (Fudan University)

  • Jinsen Zhang

    (Fudan University)

  • Xin Gao

    (Shanghai Universal Medical Imaging Diagnostic Center)

  • Li Zhu

    (Shanghai Jiao Tong University)

  • Guoping Liu

    (Fudan University)

  • Maozhi Ren

    (Chengdu National Agricultural Science and Technology Center)

  • Jianbo Xiao

    (Instituto de Agroecoloxía e Alimentación (IAA) – CITEXVI)

  • Fayong Zhang

    (Fudan University)

  • Shaojie Ma

    (Chinese Academy of Sciences)

  • Rui Zhao

    (Fudan University
    Children’s Hospital of Shanghai
    Hainan Women and Children’s Medical Center)

  • Xinyu Mei

    (Tongji University)

  • Dashi Qi

    (Tongji University
    Fudan University)

Abstract

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-1α/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.

Suggested Citation

  • Chuantao Fang & Xiaodan Zhang & Lin Yang & Licheng Sun & Yujia Lu & Yi Liu & Jingjing Guo & Min Wang & Yanfeng Tan & Jinsen Zhang & Xin Gao & Li Zhu & Guoping Liu & Maozhi Ren & Jianbo Xiao & Fayong Z, 2025. "Transcriptomic and morphologic vascular aberrations underlying FCDIIb etiology," Nature Communications, Nature, vol. 16(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58535-6
    DOI: 10.1038/s41467-025-58535-6
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