Evidence map›Paper›PMID 30298209›Full record

ArticleArchives of toxicology2018

Major changes of cell function and toxicant sensitivity in cultured cells undergoing mild, quasi-natural genetic drift.

Simon Gutbier, Patrick May, Sylvie Berthelot, Abhimanyu Krishna, Timo Trefzer, Mehri Behbehani, Liudmila Efremova, Johannes Delp, Gerhard Gstraunthaler, Tanja Waldmann and 1 more

Erratum issuedOpen access · hybridAbstract readComparative Study
In one paragraph

Article in Archives of toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 44 citations in OpenAlex.

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  10. Memory effects of prior subculture may impact the quality of multiomic perturbation profiles.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  17. LUHMES Cells: Phenotype Refinement and Development of an MPPInternational journal of molecular sciences · 2023
    Article
  18. Article
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  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Simon GutbierDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Patrick MayLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Sylvie BerthelotDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Abhimanyu KrishnaLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
Timo TrefzerDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Mehri BehbehaniDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Liudmila EfremovaDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Johannes DelpDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Gerhard GstraunthalerDivision of Physiology, Innsbruck Medical University, Schöpfstraße 41/1, 6020, Innsbruck, Austria.
Tanja WaldmannDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany.
Marcel LeistDepartment for in vitro toxicology and biomedicine (Doerenkamp-Zbinden chair), University of Konstanz, PO Box M657, 78457, Konstanz, Germany. Marcel.Leist@uni-konstanz.de.
University of Konstanz · DEUniversity of Luxembourg · LUInnsbruck Medical University · AT

Funding

European Research Council EC681002
6 · The paper itself

Abstract

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.

Indexed as

Genetic Drift1-Methyl-4-phenylpyridiniumCell DifferentiationCell LineCells, CulturedDopamine Plasma Membrane Transport ProteinsDopaminergic NeuronsDown-RegulationHumansReproducibility of ResultsTyrosine 3-MonooxygenaseWhole Genome Sequencing1-Methyl-4-phenylpyridiniumDopamine Plasma Membrane Transport ProteinsTyrosine 3-MonooxygenaseCell stabilityDopamine transporter, genome comparison, genotype-phenotype correlationHuman genome

Identifiers

PMID30298209
PMCPMC6290691
OpenAlexW2897798884

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.