Abstract：
The iPSC-derived 3D models are considered to be a connective link between 2D culture and in vivo studies. However, the sensitivity of such 3D models is yet to be established. We assessed the sensitivity of the hiPSC-derived 3D spheroids against 2D cultures of neural progenitor cells. The sub-toxic dose of Sodium Arsenite (SA) was used to investigate the alterations in miRNA-proteins in both systems. Though SA exposure induced significant alterations in the proteins in both 2D and 3D systems, these proteins were uncommon except for 20 proteins. The number and magnitude of altered proteins were higher in the 2D system compared to 3D. The association of dysregulated miRNAs with the target proteins showed their involvement primarily in mitochondrial bioenergetics, oxidative and ER stress, transcription and translation mechanism, cytostructure, etc., in both culture systems. Further, the impact of dysregulated miRNAs and associated proteins on these functions and ultrastructural changes was compared in both culture systems. The ultrastructural studies revealed a similar pattern of mitochondrial damage, while the cellular bioenergetics studies confirm a significantly higher energy failure in the 2D system than to 3D. Such a higher magnitude of changes could be correlated with a higher amount of internalization of SA in 2D cultures than in 3D spheroids. Our findings demonstrate that a 2D culture system seems better responsive than a 3D spheroid system against SA exposure.
摘要：
iPSC衍生的3D模型被认为是2D培养和体内研究之间的联系。然而,这种3D模型的敏感性尚未建立。我们评估了hiPSC衍生的3D球体对神经祖细胞2D培养物的敏感性。亚毒性剂量的亚砷酸钠（SA）用于研究两种系统中miRNA蛋白的变化。尽管SA暴露会导致2D和3D系统中蛋白质的显着变化，除了20种蛋白质外，这些蛋白质并不常见。与3D相比，2D系统中改变的蛋白质的数量和幅度更高。失调的miRNA与靶蛋白的关联显示它们主要参与线粒体生物能学,氧化和ER应激，转录和翻译机制，细胞结构，等。,在两种文化体系中。Further,在两个培养系统中比较了失调的miRNAs和相关蛋白对这些功能和超微结构变化的影响.超微结构研究揭示了类似的线粒体损伤模式，而细胞生物能量学研究证实2D系统中的能量失效明显高于3D系统。与3D球状体相比，这种更高的变化幅度可能与2D培养物中更高的SA内在化量相关。我们的发现表明，2D培养系统似乎比3D球体系统对SA暴露的反应更好。
