Article (Scientific journals)
Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift
Gutbier, Simon; May, Patrick; Berthelot, Sylvie et al.
2018In Archives of Toxicology
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Keywords :
Human Genome; Cell stability; Dopmaine Transporter
Abstract :
[en] Genomic drift affects the functional properties of cell lines, and the reproducibility of data from in vitro studies. While chromosomal aberrations and mutations in single pivotal genes are well explored, little is known about effects of minor, possibly pleiotropic, genome changes. We addressed this question for the human dopaminergic neuronal precursor cell line LUHMES by comparing two subpopulations (SP) maintained either at the American-Type-Culture-Collection (ATCC) or by the original provider (UKN). Drastic differences in susceptibility towards the specific dopaminergic toxicant 1-methyl-4-phenylpyridinium (MPP+) were observed. Whole-genome sequencing was performed to identify underlying genetic differences. While both SP had normal chromosome structures, they displayed about 70 differences on the level of amino acid changing events. Some of these differences were confirmed biochemically, but none offered a direct explanation for the altered toxicant sensitivity pattern. As second approach, markers known to be relevant for the intended use of the cells were specifically tested. The “ATCC” cells rapidly down-regulated the dopamine-transporter and tyrosine-hydroxylase after differentiation, while “UKN” cells maintained functional levels. As the respective genes were not altered themselves, we conclude that polygenic complex upstream changes can have drastic effects on biochemical features and toxicological responses of relatively similar SP of cells.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Genetics & genetic processes
Author, co-author :
Gutbier, Simon
May, Patrick  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Berthelot, Sylvie
Krishna, Abhimanyu
Trefzer, Timo
Behbehani, Mehri
Effremova, Liudmilla
Delp, Johannes
Gstraunthaler, Gerhard
Waldmann, Tanja
Leist, Marcel
External co-authors :
Language :
Title :
Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift
Publication date :
08 October 2018
Journal title :
Archives of Toxicology
Publisher :
Springer, Germany
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 11 October 2018


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