Effect of EBV-Transformation on Oxidative Phosphorylation Physiology in Human Cell lines
Effect of EBV-Transformation on Oxidative Phosphorylation Physiology in Human Cell lines
复制标题
EBV 转化对人类细胞系氧化磷酸化生理学的影响
DOI：
10.1101/2019.12.16.878025
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发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Crawford, Douglas
中科院分区：
文献类型：
--
作者：
Weinstein, Rachel N.;Crawford, Douglas
1,000个人类基因组计划中的1,000多个细胞系是否代表了细胞生理学和遗传变异重要性的宝贵资源？对超过1,000个个体的基因组进行了测序，并收集了他们的白色血细胞，进行了永生化和冷冻保存。虽然对1,000个人类基因组中的核苷酸变异进行了大量研究，但这些人类生理学的定量测量很少。幸运的是，可以对他们的永生化和保存的细胞进行生理措施。然而，这些人白色血细胞通过用EB病毒（EBV转化的淋巴母细胞样细胞系（LCL））转化而永生化。这种转化将病毒基因组整合到人类基因组中，并可能影响个体之间的重要生物学差异。我们在这里解决的问题是，这种转换是否显着改变了细胞生理学，使复制个体显着不同，也就是说，这种转换是否增加了显着水平的方差。为了研究EBV转化对重复转化之间变化的影响，我们定量了来自6个具有4个单独和独立EBV转化的个体的LCL中的氧化磷酸化（OxPhos）代谢。我们研究了OxPhos，因为它对能量产生至关重要，并且该途径中的突变是大多数先天性代谢疾病的原因。这里提供的数据表明，EBV转化有一个小但显著的影响。尽管由于转化的显着变化，有更大的和显着的变化，个人之间的OxPhos代谢。此外，EBV转化效应影响特定的OxPhos性状：例如，缺乏mtDNA编码蛋白的复合物II可能对EBV效应更敏感。总之，虽然EBV转化改变OxPhos，但其影响很小，并影响特定的OxPhos性状，我们能够检测到个体之间的统计学显着差异。
Do the over 1,000 individuals cell lines that are part of the 1,000 Human Genomes Project represent a valuable resource for cellular physiology and the importance of genetic variation. For the over 1,000 individuals their genomes were sequenced, and their white blood cells collected, immortalized and cryopreserved. While much research exists on the nucleotide variation in the 1,000 Human Genomes, there are few quantitative measures of these humans’ physiologies. Fortunately, physiological measures can be done on their immortalized and preserved cells. However, these human white blood cells were immortalized by transforming them with the Epstein-Barr virus (EBV-transformed lymphoblastoid cell lines (LCL)). This transformation integrates the viral genome into the human genome and potentially affects important biological differences among individuals. The question we address here is whether this transformation significantly alters the cellular physiology so that replicate individuals are significantly different—that is, does this transformation adds significant level of variance. To investigate the effect of EBV-transformation on the variation among replicate transformation, we quantified oxidative phosphorylation (OxPhos) metabolism in LCLs from six individuals with 4 separate and independent EBV-transformations. We examined OxPhos because it is critical for energy production, and mutations in this pathway are responsible most inborn metabolic diseases. The data presented here demonstrate that there is a small but significant effect of EBV-transformations. In spite of significant variation due to transformation, there is greater and significant variation among individuals in their OxPhos metabolism. Additionally, EBV transformation effects affected specific OxPhos traits: e.g. Complex II, which lacks mtDNA-encoded proteins, may be more sensitive to EBV effects. Inconclusion, while EBV-transformation alters OxPhos, its effect is small and affected specific OxPhos traits and we are able to detect statistically significant variation among individuals.
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