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人源细胞系中 APOE 基因型状态的变异性:细胞培养研究中的一个关注点?

Variability in APOE genotype status in human-derived cell lines: a cause for concern in cell culture studies?

机构信息

Department of Biochemistry, Centre for Life Sciences, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.

出版信息

Genes Nutr. 2014 Jan;9(1):364. doi: 10.1007/s12263-013-0364-4. Epub 2013 Dec 3.

DOI:10.1007/s12263-013-0364-4
PMID:24297645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3896624/
Abstract

Although cell culture studies have provided landmark discoveries in the basic and applied life sciences, it is often under-appreciated that cells grown in culture are prone to generating artifacts. Here, we introduce the genotype status (exemplified by apolipoprotein E) of human-derived cells as a further important parameter that requires attention in cell culture experiments. Epidemiological and clinical studies indicate that variations from the main apolipoprotein E3/E3 genotype might alter the risk of developing chronic diseases, especially neurodegeneration, cardiovascular disease, and cancer. Whereas the apolipoprotein E allele distribution in human populations is well characterized, the apolipoprotein E genotype of human-derived cell lines is only rarely considered in interpreting cell culture data. However, we find that primary and immortalized human cell lines show substantial variation in their apolipoprotein E genotype status. We argue that the apolipoprotein E genotype status and corresponding gene expression level of human-derived cell lines should be considered to better avoid (or at least account for) inconsistencies in cell culture studies when different cell lines of the same tissue or organ are used and before extrapolating cell culture data to human physiology in health and disease.

摘要

尽管细胞培养研究为基础和应用生命科学提供了具有里程碑意义的发现,但人们往往没有意识到,在培养中的细胞容易产生假象。在这里,我们介绍了人类来源的细胞的基因型状态(以载脂蛋白 E 为例),这是细胞培养实验中需要注意的另一个重要参数。流行病学和临床研究表明,载脂蛋白 E3/E3 主要基因型的变异可能会改变患慢性疾病(尤其是神经退行性疾病、心血管疾病和癌症)的风险。尽管人类群体中的载脂蛋白 E 等位基因分布特征良好,但在解释细胞培养数据时,很少考虑人类来源的细胞系的载脂蛋白 E 基因型。然而,我们发现原代和永生化的人类细胞系在载脂蛋白 E 基因型状态上存在很大差异。我们认为,应该考虑人类来源的细胞系的载脂蛋白 E 基因型状态和相应的基因表达水平,以更好地避免(或至少解释)在使用同一组织或器官的不同细胞系时细胞培养研究中的不一致性,并在将细胞培养数据外推到健康和疾病中的人体生理学之前。

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本文引用的文献

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Apolipoprotein E genotype affects tissue metallothionein levels: studies in targeted gene replacement mice.载脂蛋白 E 基因型影响组织金属硫蛋白水平:靶向基因替换小鼠的研究。
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