Back to overview

Multi-omic measurements of heterogeneity in HeLa cells across laboratories.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Bena FS, Zhou h, Dehio C, Testa G, Saez-Rodriguez J, Antonarakis SE, Hardt WD, Aebersold R, Liu Y, Mi Y, Mueller T, Kreibich S, Williams EG, Van Drogen A, Borel C, Frank M, Germain PL, Bludau I, Mehnert M, Seifert M, Emmenlauer M, Sorg I, Bezrukov F,
Project Bacterial Type IV Secretion (T4S): Cellular, Molecular, and Evolutionary Basis of the Subversion of Host Cell Functions by Translocated Effector Proteins
Show all

Original article (peer-reviewed)

Journal Nature biotechnology
Volume (Issue) 37(3)
Page(s) 314 - 322
Title of proceedings Nature biotechnology
DOI 10.1038/s41587-019-0037-y

Open Access

Type of Open Access Green OA Embargo (Freely available via Repository after an embargo)


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.