使用定向分化和转录重编程生成hiPSC衍生的脑微血管内皮细胞
Aomeng Cui1, Ronak Patel2, Patrick Bosco2
1Department of Neurology (A.C., U.A., D.A.), Columbia University Irving Medical Center, New York, NY.
Arteriosclerosis, thrombosis, and vascular biology
|November 25, 2025
概括
研究人员从诱导的多能干干细胞 (iPSC) 中开发了重编程的大脑微血管内皮细胞 (rBMEC),以更好地模拟人类血脑屏障 (BBB). 这些rBMECs表现出增强的BBB特性和特定于大脑的转录组,有助于阿尔茨海默病研究.
科学领域:
- 神经科学是一个神经科学.
- 干细胞生物学 干细胞生物学
- 血管生物学 血管生物学
背景情况:
- 人类血脑屏障 (BBB) 的建模具有挑战性,原因是产生功能诱导多能干细胞 (iPSC) 衍生的脑微血管内皮细胞 (BMEC) 的局限性.
- 现有的方法无法完全复制关键的BMEC功能和大脑内皮细胞的特定基因表达模式.
研究的目的:
- 使用iPSCs开发一种强大的协议,用于生成具有增强血脑屏障特性的重编程BMEC (rBMEC).
- 在3D神经血管模型中调查家族性阿尔茨海默病突变对BBB完整性和炎症反应的影响.
主要方法:
- 人类iPSCs的定向分化与转录因子FOXF2和ZIC3的过度表达相结合,产生rBMECs.
- 使用免疫光,功能测试和大量RNA测序进行表征.
- 在微流体平台上与iPSC衍生的星细胞和周细胞共同培养rBMEC,以创建一个3D神经血管单元.
主要成果:
- rBMECs表现出BBB转录组的一个子集,改善了屏障功能,减少了转细胞体,和可比的P-糖蛋白活性与初级BMECs.
- 由rBMECs,星细胞和周细胞组成的3D神经血管系统表现出强大的BBB特性.
- 在rBMECs中家族性阿尔茨海默病突变 (APP V717I) 导致屏障完整性降低和炎症标志物增加,与寡合氨基酸β-β效应不同.
结论:
- 开发的协议成功地产生了具有显著BBB特性和脑特异性转录组的rBMEC.
- 来自iPSC的3D神经血管单元模型有效地回顾了体内人类BBB的各个方面.
- 该APP V717I突变独立影响BBB属性和炎症状态,提供了对阿尔茨海默病病原体的见解.
相关概念视频
01:13Induced Pluripotent Stem Cells
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore called induced pluripotent stem...
01:22iPS Cell Differentiation
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.