Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Resolution. Schaeffer and Pacholko et al.

These Imaris image files accompany the raw microscopy and Imaris image data in version 1, accessed at 10.17632/8jkmn4p2px.1. This data was uploaded separately due to file size limitations.

Hypertension is a leading cause of cognitive impairment, attributed to cerebrovascular insufficiency, blood-brain barrier disruption, and white matter damage. However, how hypertension affects brain cells remains unclear. Using scRNA-seq in a mouse model of hypertension induced by angiotensin II, a peptide involved in human hypertension, we mapped neocortical transcriptomic changes before (3 days) and after (42 days) onset of neurovascular and cognitive deficits. Surprisingly, endothelial transport disruption and senescence, stalled oligodendrocyte differentiation, and interneuronal hypofunction and network imbalance emerged after 3 days, attributable to angiotensin II signaling. By 42 days, when cognitive impairment becomes apparent, deficits in myelination and axonal conduction, as well as neuronal mitochondrial dysfunction, developed. These findings reveal a previously unrecognized early vulnerability of endothelial cells, interneurons, and oligodendrocytes, and provide the molecular bases for subsequent neurovascular dysfunction and cognitive impairment in hypertension. These data constitute a valuable resource for future mechanistic studies and therapeutic target validation.

本Imaris成像文件（Imaris）与版本1的原始显微成像数据及Imaris成像数据配套，该数据集可通过DOI：10.17632/8jkmn4p2px.1获取，因文件体积限制，本部分数据单独上传。

高血压是认知功能障碍的首要致病诱因，其病理机制与脑血管灌注不足、血脑屏障（blood-brain barrier）破坏及白质损伤密切相关，但高血压如何调控脑细胞功能的具体机制至今尚未明确。

本研究针对由血管紧张素II（angiotensin II，一种参与人类高血压发病的肽类物质）诱导的高血压小鼠模型开展单细胞RNA测序（scRNA-seq），绘制了神经血管与认知功能缺损发作前（3天）及发作后（42天）的新皮层转录组变化图谱。令人意外的是，造模3天后即可观察到内皮细胞转运功能障碍与衰老、少突胶质细胞分化停滞，以及中间神经元功能低下与神经网络失衡，上述变化均由血管紧张素II信号通路介导。至造模42天，即认知功能缺损显现时，小鼠出现髓鞘形成缺陷、轴突传导功能异常及神经元线粒体功能障碍。

本研究结果揭示了内皮细胞、中间神经元与少突胶质细胞此前未被认知的早期易损性，并为高血压后续神经血管功能异常与认知功能障碍提供了分子层面的理论基础。本数据集可为后续机制研究及治疗靶点验证提供宝贵的科研资源。