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从诱导的多能干干细胞中区分内脏感官质器官

Kyusik Ahn^1,2, Hwee-Seon Park^1,3, Sieun Choi⁴

¹Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

|October 22, 2024

概括

诱导的多能干细胞可以产生内脏感官神经元来模拟肠-神经-大脑轴. 这种器官模型表明,内脏感官神经元可能将肠粉样蛋白和病理与阿尔茨海默病联系起来.

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
胃肠病学胃肠病学

背景情况:

肠-神经-大脑轴在神经疾病中起着至关重要的作用.
了解内脏感官神经元 (VSN) 的参与是解开这些复杂相互作用的关键.
诱导多能干细胞 (iPSCs) 为产生疾病建模的特定神经元类型提供了一个有希望的来源.

研究的目的:

建立一个区分人类iPSC衍生的内脏感官质器官 (VSGOs) 的协议.
开发肠-神经-大脑轴的体外模型,以研究神经系统疾病,特别是阿尔茨海默病.
研究VSN在肠道衍生病理分子向大脑传播中的作用.

主要方法:

人类iPSCs分化为VSGO.
使用正规的VSN标记物和单细胞RNA测序来对VSGO进行表征.
在微流体装置上将VSGO与人类结肠器官集成,以创建一个芯片上的轴模型.
该模型应用于研究阿尔茨海默病的病理学,包括粉样蛋白和蛋白的传播.

主要成果:

成功生成了VSGO,显示了正规的VSN标记.
单细胞RNA测序证实了VSGO的异质分子特征和发育轨迹,与本地VSN保持一致.
芯片上的轴模型表明,VSN可能会调解肠道衍生的粉样蛋白和蛋白向大脑的传播.
这种传播被证明取决于APOE4和LRP1.
来自患者的iPSC模型与临床数据有很强的相关性.

结论:

人类iPSC衍生的VSGO为研究肠-神经-大脑轴提供了有价值的工具.
VSN代表了与阿尔茨海默氏症相关的病理的肠-脑通信的潜在途径.
开发的芯片轴模型,利用患者衍生的iPSC,对个性化疾病建模和治疗标识有希望.

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