会影响人类诱导的多能干细胞分化为胆运动神经元
M Chiara Perego1, Benjamin D McMichael2, Nicholas R McMurry1
1Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
Toxics
|August 25, 2023
概括
环境暴露会扰乱人类干细胞中的运动神经元发育,损害胆突触功能,并暗示神经发育的风险.
科学领域:
- 发育神经生物学的发展神经生物学
- 干细胞生物学 干细胞生物学
- 环境毒理学环境毒理学
背景情况:
- 在发育过程中接触可能会对神经发育和运动活动产生负面影响.
- 实验室研究表明,会抑制感觉神经元和骨肌肉的分化.
- 了解对人类运动神经元发育的影响至关重要.
研究的目的:
- 研究暴露对人类诱导的多能干细胞 (iPS) 细胞分化成运动神经元的影响.
- 为了分析对运动神经元发育过程中的胆突触通路的影响.
- 评估暴露对发育中的运动神经元的功能后果.
主要方法:
- 人类iPS细胞在28天的时间内分化为运动神经元,同时暴露于 (高达0.5μM).
- 基因表达分析 (RT-qPCR,RNA测序) 在不同分化阶段 (第6,12,18,28天) 进行.
- 在成熟的运动神经元中测量了蛋白质表达 (西部斑) 和神经元长度.
主要成果:
- 暴露改变了神经前体标记 (NES,SOX1) 和运动神经元分化标记 (CHAT) 的转录水平.
- RNA测序揭示了胆固醇突触通路的损伤,降低了对乙胆合成,运输和降解的基因的调节.
- 暴露减少了MAP2和ChAT的蛋白质表达,并在成熟的运动神经元中减少了神经元长度.
结论:
- 环境相关的含量会破坏人类iPS细胞分化成运动神经元.
- 暴露会损害胆突触通路,这表明发育中的运动神经元中的胆功能受损.
- 这些发现凸显了暴露对神经发育和运动神经元功能的潜在风险.
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