精神分裂症内皮细胞表现出更高的透性和改变患者衍生器官的血管生成模式
Isidora Stankovic1, Michael Notaras1, Paul Wolujewicz1
1Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Translational psychiatry
|January 23, 2024
概括
精神分裂症 (SCZ) 器官表现出增加的血管细胞和改变的基因表达,这表明早期大脑发育中的血管功能障碍有助于SCZ. 这突出了大脑微血管细胞在SCZ病因学中的潜在作用.
科学领域:
- 神经科学是一个神经科学.
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 精神分裂症 (SCZ) 是一种复杂的神经发育障碍,其起源不明.
- 在早期大脑发育期间SCZ神经病理学中,内皮和血管功能障碍的作用在很大程度上是未知的.
研究的目的:
- 在关键发育时期使用患者衍生诱导多能干细胞 (iPSC) 建模SCZ神经病理学.
- 确定细胞特异性疾病特征,并研究血管细胞对SCZ的贡献.
主要方法:
- 从SCZ患者衍生的iPSC和健康对照 (CTRL) 来生成3D大脑器官.
- 单细胞RNA测序以分析细胞特异性基因表达.
- 微血管结构的量化和内皮细胞透性的评估.
主要成果:
- 与CTRL器官相比,SCZ器官中内皮细胞的比例更高.
- SCZ内皮细胞表现出与血管形成,血管调节和炎症相关的丰富基因表达.
- 在SCZ有机体中,PECAM1+微血管结构的长度和数量增加,内皮细胞透率提高.
结论:
- 来自患者的SCZ有机体显示出改变的内皮细胞基因表达,增加的微血管结构和增强的透性.
- 这些发现表明,大脑的微血管细胞可能通过在发育过程中影响血脑屏障 (BBB) 透性而导致SCZ病因.
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