Krishna Abhimanyu, Biryukov Maria, Trefois Christophe, Antony Paul M A, Hussong Rene, Lin Jake, Heinäniemi Merja, Glusman Gustavo, Köglsberger Sandra, Boyd Olga, van den Berg Bart H J, Linke Dennis, Huang David, Wang Kai, Hood Leroy, Tholey Andreas, Schneider Reinhard, Galas David J, Balling Rudi, May Patrick
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Campus Belval, 7, avenue des Hauts-Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
BMC Genomics. 2014 Dec 20;15(1):1154. doi: 10.1186/1471-2164-15-1154.
The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson's disease, the relevance of this cellular model in the context of Parkinson's disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated.
We have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD.
The systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson's disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer's disease but lower than for Huntington's disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments.
人神经母细胞瘤细胞系SH-SY5Y是神经毒性、氧化应激和神经退行性疾病相关研究中常用的细胞系。尽管该细胞系常被用作帕金森病的细胞模型，但在帕金森病（PD）及其他神经退行性疾病背景下，此细胞模型的相关性尚未得到系统评估。
我们采用系统基因组学方法，通过全基因组测序来确定SH-SY5Y细胞系的遗传内容，以此对该细胞系进行特征描述，并利用转录组学和蛋白质组学数据来确定分子间的相关性。此外，我们使用网络分析方法整合基因组变异，以评估SH-SY5Y细胞系在包括PD在内的神经退行性疾病背景下进行扰动实验的适用性。
系统基因组学方法在不同生物水平（DNA、RNA和蛋白质浓度）上显示出一致性。SH-SY5Y基因组中大多数属于主要帕金森病通路和模块的基因是完整的。具体而言，每个与PD相关的分析基因在SH-SY5Y中至少有一个完整拷贝。对于功能丧失扰动实验，疾病特异性网络分析方法将SH-SY5Y针对PD的遗传完整性排名高于阿尔茨海默病，但低于亨廷顿舞蹈症和肌萎缩侧索硬化症。
