Format

Send to

Choose Destination
Nat Biotechnol. 2019 Mar;37(3):314-322. doi: 10.1038/s41587-019-0037-y. Epub 2019 Feb 18.

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

Author information

1
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA. yansheng.liu@yale.edu.
2
Yale Cancer Biology Institute, Yale University, West Haven, CT, USA. yansheng.liu@yale.edu.
3
Heidelberg University, Faculty of Biosciences, Heidelberg, Germany.
4
Joint Research Center for Computational Biomedicine (JRC-COMBINE), Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
5
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
6
Institute of Microbiology, ETH Zurich, Zurich, Switzerland.
7
Department of Genetic Medicine and Development, University of Geneva Medical School, and University Hospitals of Geneva, Geneva, Switzerland.
8
IEO, European Institute of Oncology IRCCS, Milan, Italy.
9
Institute for Medical Informatics and Biometry, Carl Gustav Carus Faculty of Medicine, Technische Universit├Ąt Dresden, Dresden, Germany.
10
National Center for Tumor Diseases, Dresden, Germany.
11
Biozentrum, University of Basel, Basel, Switzerland.
12
Service of Genetic Medicine, University Hospitals of Geneva, Geneva, Switzerland.
13
Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
14
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
15
Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Bioquant Heidelberg, Germany.
16
iGE3 Institute of Genetics and Genomics of Geneva, Geneva, Switzerland.
17
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.
18
Faculty of Science, University of Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.

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.

PMID:
30778230
DOI:
10.1038/s41587-019-0037-y
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center