TY - JOUR
T1 - Multi-omic measurements of heterogeneity in HeLa cells across laboratories
AU - Liu, Yansheng
AU - Mi, Yang
AU - Mueller, Torsten
AU - Kreibich, Saskia
AU - Williams, Evan G.
AU - Van Drogen, Audrey
AU - Borel, Christelle
AU - Frank, Max
AU - Germain, Pierre Luc
AU - Bludau, Isabell
AU - Mehnert, Martin
AU - Seifert, Michael
AU - Emmenlauer, Mario
AU - Sorg, Isabel
AU - Bezrukov, Fedor
AU - Bena, Frederique Sloan
AU - Zhou, Hu
AU - Dehio, Christoph
AU - Testa, Giuseppe
AU - Saez-Rodriguez, Julio
AU - Antonarakis, Stylianos E.
AU - Hardt, Wolf Dietrich
AU - Aebersold, Ruedi
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061731215&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061731215&partnerID=8YFLogxK
U2 - 10.1038/s41587-019-0037-y
DO - 10.1038/s41587-019-0037-y
M3 - Article
C2 - 30778230
AN - SCOPUS:85061731215
VL - 37
SP - 314
EP - 322
JO - Biotechnology
JF - Biotechnology
SN - 1087-0156
IS - 3
ER -