Evidence map›Paper›PMID 27188386›Full record

ArticleArchives of toxicology2017

Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Tox

Vaibhav Shinde, Lisa Hoelting, Sureshkumar Perumal Srinivasan, Johannes Meisig, Kesavan Meganathan, Smita Jagtap, Marianna Grinberg, Julia Liebing, Nils Bluethgen, Jörg Rahnenführer and 12 more

Open access · hybridAbstract read
In one paragraph

Article in Archives of toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
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  11. Optimization of the TeraTox Assay for Preclinical Teratogenicity Assessment.Toxicological sciences : an official journal of the Society of Toxicology · 2022
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  16. Testing of female reproductive disorders.Archives of toxicology · 2020
    Article
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  19. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 6 institutions in 1 country.

Vaibhav ShindeInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Lisa HoeltingDoerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Box: M657, 78457, Constance, Germany.
Sureshkumar Perumal SrinivasanInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Johannes MeisigInstitute of Pathology, Charité Universitätsmedizin, 10117, Berlin, Germany.
Kesavan MeganathanInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Smita JagtapInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Marianna GrinbergDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Julia LiebingLeibniz Research Centre for Working Environment and Human Factors at the Technical, University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.
Nils BluethgenInstitute of Pathology, Charité Universitätsmedizin, 10117, Berlin, Germany.
Jörg RahnenführerDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Eugen RempelDepartment of Statistics, TU Dortmund University, Dortmund, Germany.
Regina StoeberLeibniz Research Centre for Working Environment and Human Factors at the Technical, University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.
Stefan SchildknechtDoerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Box: M657, 78457, Constance, Germany.
Sunniva FörsterDoerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Box: M657, 78457, Constance, Germany.
Patricio GodoyLeibniz Research Centre for Working Environment and Human Factors at the Technical, University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.
Christoph van ThrielLeibniz Research Centre for Working Environment and Human Factors at the Technical, University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany.
John Antonydas GasparInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Jürgen HeschelerInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany.
Tanja WaldmannDoerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Box: M657, 78457, Constance, Germany.
Jan G HengstlerLeibniz Research Centre for Working Environment and Human Factors at the Technical, University of Dortmund (IfADo), Ardeystrasse 67, 44139, Dortmund, Germany. hengstler@ifado.de.
Marcel LeistDoerenkamp-Zbinden Chair for In Vitro Toxicology and Biomedicine, University of Konstanz, Box: M657, 78457, Constance, Germany. marcel.leist@uni-konstanz.de.
Agapios SachinidisInstitute of Neurophysiology and Centre for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Robert-Koch-Str. 39, 50931, Cologne, Germany. a.sachinidis@uni-koeln.de.
University of Cologne · DETU Dortmund University · DEUniversity of Konstanz · DECharité - Universitätsmedizin Berlin · DELeibniz Research Centre for Working Environment and Human Factors · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Stem cell-based in vitro test systems can recapitulate specific phases of human development. In the UKK test system, human pluripotent stem cells (hPSCs) randomly differentiate into cells of the three germ layers and their derivatives. In the UKN1 test system, hPSCs differentiate into early neural precursor cells. During the normal differentiation period (14 days) of the UKK system, 570 genes [849 probe sets (PSs)] were regulated >fivefold; in the UKN1 system (6 days), 879 genes (1238 PSs) were regulated. We refer to these genes as 'developmental genes'. In the present study, we used genome-wide expression data of 12 test substances in the UKK and UKN1 test systems to understand the basic principles of how chemicals interfere with the spontaneous transcriptional development in both test systems. The set of test compounds included six histone deacetylase inhibitors (HDACis), six mercury-containing compounds ('mercurials') and thalidomide. All compounds were tested at the maximum non-cytotoxic concentration, while valproic acid and thalidomide were additionally tested over a wide range of concentrations. In total, 242 genes (252 PSs) in the UKK test system and 793 genes (1092 PSs) in the UKN1 test system were deregulated by the 12 test compounds. We identified sets of 'diagnostic genes' appropriate for the identification of the influence of HDACis or mercurials. Test compounds that interfered with the expression of developmental genes usually antagonized their spontaneous development, meaning that up-regulated developmental genes were suppressed and developmental genes whose expression normally decreases were induced. The fraction of compromised developmental genes varied widely between the test compounds, and it reached up to 60 %. To quantitatively describe disturbed development on a genome-wide basis, we recommend a concept of two indices, 'developmental potency' (D

Indexed as

AnimalsCell DifferentiationCell LineEmbryonic Stem CellsGene Expression Regulation, DevelopmentalHumansMicePluripotent Stem CellsStem CellsTeratogensToxicity TestsTranscriptomeTeratogensDevelopmental toxicityGenomics biomarkersHuman stem cellsIn vitro test systemsTranscriptome

Identifiers

PMID27188386
PMCPMC5306084
OpenAlexW2407121306

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.