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.

Multi-omic measurements of heterogeneity in HeLa cells across laboratories / Y. Liu, Y. Mi, T. Mueller, S. Kreibich, E.G. Williams, A. Van Drogen, C. Borel, M. Frank, P. Germain, I. Bludau, M. Mehnert, M. Seifert, M. Emmenlauer, I. Sorg, F. Bezrukov, F.S. Bena, H. Zhou, C. Dehio, G. Testa, J. Saez-Rodriguez, S.E. Antonarakis, W. Hardt, R. Aebersold. - In: NATURE BIOTECHNOLOGY. - ISSN 1087-0156. - 37:3(2019 Mar), pp. 314-322.

Multi-omic measurements of heterogeneity in HeLa cells across laboratories

P. Germain;G. Testa;
2019

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.
Settore BIO/11 - Biologia Molecolare
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore BIO/13 - Biologia Applicata
Settore BIO/18 - Genetica
Settore MED/03 - Genetica Medica
Settore MED/04 - Patologia Generale
Settore BIO/10 - Biochimica
feb-2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/626367
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