赫拉
表型
细胞培养
蛋白质组
转录组
生物
计算生物学
细胞生物学
基因
遗传学
基因表达
作者
Yansheng Liu,Meizhu Yang,Torsten Mueller,Saskia Kreibich,Evan G. Williams,Audrey van Drogen,Christelle Borel,Max Frank,Pierre‐Luc Germain,Isabell Bludau,Martin Mehnert,Michael Seifert,Mario Emmenlauer,Isabel Sorg,Fedor Bezrukov,Frédérique Béna,Hu Zhou,Christoph Dehio,Giuseppe Testa,Julio Sáez-Rodríguez,Stylianos E. Antonarakis,Wolf‐Dietrich Hardt,Ruedi Aebersold
标识
DOI:10.1038/s41587-019-0037-y
摘要
Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. We cultured cells in uniform conditions and profiled genome-wide copy numbers, mRNAs, proteins and protein turnover rates in each cell line. We discovered substantial heterogeneity between HeLa variants, especially between lines of the CCL2 and Kyoto varieties, and observed progressive divergence within a specific cell line over 50 successive passages. Genomic variability has a complex, nonlinear effect on transcriptome, proteome and protein turnover profiles, and proteotype patterns explain the varying phenotypic response of different cell lines to Salmonella infection. These findings have implications for the interpretation and reproducibility of research results obtained from human cultured cells. Systems-wide analysis of HeLa cell lines from 13 labs identifies substantial molecular and phenotypic variability.
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