Multi-omic measurements of heterogeneity in HeLa cells across laboratories

Yansheng Liu, Yang Mi, 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, Frederique Sloan Bena, Hu Zhou, Christoph Dehio, Giuseppe Testa, Julio Saez-RodriguezStylianos E. Antonarakis, Wolf Dietrich Hardt, Ruedi Aebersold

    Research output: Contribution to journalArticlepeer-review

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)314-322
    Number of pages9
    JournalNature biotechnology
    Volume37
    Issue number3
    Early online date18 Feb 2019
    DOIs
    Publication statusPublished - 1 Mar 2019

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