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检查iPSC衍生的运动神经元变异性和基因组稳定性监测作为一种解决方案

Finbar Gaffey¹, David McCoull², Egle Vaitone²

¹LifeArc, Accelerator Building, Open Innovation Campus, Stevenage, SG1 2FX, UK. finbar.gaffey@lifearc.org.

Scientific reports

|November 12, 2025

概括

诱导多能干细胞 (iPSC) 衍生的运动神经元 (MN) 分化中的变异性主要是由于非遗传因素,而不是细胞系遗传学. 在运动神经元疾病研究中,iPSCs的基因组稳定性对于可靠的mn模型至关重要.

科学领域:

干细胞生物学干细胞生物学
神经科学是一个神经科学.
药物发现药物发现

背景情况:

诱导多能干细胞 (iPSCs) 对模拟运动神经元疾病 (MNDs) 有价值.
差异化协议的变化阻碍了iPSC衍生的运动神经元 (MN) 的可复制性和可靠性.

研究的目的:

在工业环境中量化MN差异化的小分子协议中的可变性.
为了确定iPSC衍生的MNs的变异性来源.
评估iPSC基因组稳定性对差异化结果的影响.

主要方法:

分析了8条iPSC线路中的15个差异化集.
评估一个用于MN分化的小分子协议.
评估iPSC基因组不稳定性,使用针对性RT-qPCR对型异常进行评估.

主要成果:

非遗传因素 (诱导组,操作者) 是变异的主要来源,超过了遗传贡献.
iPSC的基因组不稳定性显著影响了MN的差异化效率和纯度.
基因组稳定的iPSCs产生了更可复制的分化,并改善了MN标记物表达.

结论:

对iPSC的常规基因组评估对于提高iPSC衍生的MN模型的可靠性至关重要.
提高iPSC模型可靠性可以支持MND的临床前研究和治疗开发.
标准化iPSC质量控制对于推进再生医学和疾病建模至关重要.

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