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通过对跨协议的hiPSC衍生模型的系统成像分析揭示了神经元纤维化率和纤维含量的差异

Walther Haenseler¹, Melanie Eschment^2,3, Beth Evans²

¹URPP Adaptive Brain Circuits in Development and Learning, University of Zurich, Zurich, Switzerland.

Frontiers in cell and developmental biology

|April 28, 2025

概括

人类诱导的多能干细胞 (hiPSCs) 对于研究神经发育障碍至关重要. 这项研究详细介绍了hiPSC衍生神经元中的纤维化速率和蛋白质含量,揭示了成熟和分化协议的变化.

科学领域:

神经科学是一个神经科学.
细胞生物学细胞生物学
发育生物学发展生物学

背景情况:

纤毛病是一种与初级纤毛功能障碍相关的门德尔性疾病,通常会导致神经发育问题.
人类中枢神经系统 (CNS) 组织很难获得,因此患者衍生的人类诱导多能干细胞 (hiPSCs) 对研究至关重要.
主要毛在中枢神经系统的发育和功能中起着关键作用,需要在相关的细胞模型中进行研究.

研究的目的:

系统地分析hiPSC衍生的神经干细胞 (NSC) 和神经元中的纤维化速率和纤维蛋白含量.
调查分化协议和成熟阶段如何影响hiPSC衍生神经细胞中的纤毛.
在这些模型中探索依赖的Sonic hedgehog (SHH) 信号的潜在发展窗口.

主要方法:

在多个hiPSC线上利用各种2D和3D神经元分化协议.
使用免疫光学量化纤维化速率和纤维长度.
在不同分化阶段分析了状蛋白表达 (ARL13B,INPP5E,AC3,GPR161).

主要成果:

纤维化率因细胞系和协议而异,在NSC达到峰值,随着神经元成熟而下降 (成熟神经元中低至10%).
较高的神经元密度与增加的纤维化相关.
随着成熟,观察到状蛋白表达的明显变化,包括成熟神经元中对SHH刺激的GPR161反应的丧失.

结论:

结果提供了对hiPSC衍生神经元中不同协议和成熟阶段的初级乳毛细胞的系统性表征.
强调选择适当的模型系统和控制来研究hiPSC衍生的神经元细胞中初级毛的重要性.
表明神经元发育中的依赖SHH信号的发育窗口.

关键词:

西里亚西里亚是什么意思纤维病变 (ciliopathy) 是一种纤维病变.人类iPSC (诱导多能干细胞)免疫光染色的染色方法神经元神经元的神经元

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