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TDCPP促进了亡,并抑制了人类神经干细胞中的信号通路

Ming-Rui Li¹, Guo-Rui Zhou¹, Zi-Ye Wang¹

¹State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China.

The Science of the total environment

|January 11, 2025

概括

三 (1,3-二-2-) 酸盐 (TDCPP) 通过破坏信号来损害人类神经干细胞. 这种有机阻燃剂 (OFR) 影响细胞活力,细胞循环和细胞亡,可能影响神经系统发育.

科学领域:

神经科学是一个神经科学.
毒理学毒理学毒理学
干细胞生物学干细胞生物学

背景情况:

三 (1,3-二-2-) 酸盐 (TDCPP) 是一种广泛使用的有机阻燃剂 (OFR).
以前的研究表明TDCPP可能会引起神经毒性,但潜在的机制仍然不清楚.
人类诱导多能干细胞 (hiPSCs) 衍生的神经干细胞 (hNSCs) 为调查污染物神经毒性提供了有价值的体外模型.

研究的目的:

研究TDCPP对hNSCs的神经毒性影响.
阐明TDCPP诱导的神经毒性背后的分子机制.
检查TDCPP对hNSCs信号通路的影响.

主要方法:

作为一个体外模型,利用了hiPSCs衍生的hNSCs.
评估了细胞活力,活性氧物种 (ROS) 生成,细胞周期进展和细胞亡.
进行了转录组测序和KEGG丰富分析.
研究了细胞内平衡和关键信号通路组件.

主要成果:

TDCPP显著抑制了hNSC的活力,增加了ROS的产生,诱导了S相细胞周期停止,并促进了细胞亡.
转录组分析确定了387个差异表达的基因,其中信号通路是最丰富的.
TDCPP破坏了细胞内平衡,并损害了Ca2+/CALM/CaN/CAMK信号通路,减少了NFATC2和GSK3β的表达.

结论:

在人类神经干细胞中,TDCPP对信号通路具有显著的毒性.
这些信号中断可能会对人类神经系统发育产生不利影响.
通过对关键细胞通路的影响,TDCPP对神经发育构成潜在的风险.

关键词:

神经干细胞的神经干细胞神经毒性神经毒性有机阻燃剂的阻燃剂.这就是ROSOS ROS.这就是TDCPPPPTDC.

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