A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors

Archives of Toxicology

Volumn 89, Issue 9, 2015, Pages 1599-1618

  Rempel, Eugen ^a,b   Hoelting, Lisa ^c   Waldmann, Tanja ^c   Balmer, Nina V ^c   Schildknecht, Stefan ^c   Grinberg, Marianna ^a   Das Gaspar, John Antony ^d   Shinde, Vaibhav ^d   Stöber, Regina ^e   Marchan, Rosemarie ^e   van Thriel, Christoph ^e   Liebing, Julia ^e   Meisig, Johannes ^f,g   Blüthgen, Nils ^f,g   Sachinidis, Agapios ^d   Rahnenführer, Jörg ^a   Hengstler, Jan G ^e   Leist, Marcel ^c  

^a TU DORTMUND UNIVERSITY   (Germany)

^b UNIVERSITY OF HEIDELBERG   (Germany)

^c UNIVERSITY OF KONSTANZ   (Germany)

^d UNIVERSITY OF COLOGNE   (Germany)

^e LEIBNIZ RESEARCH CENTRE FOR WORKING ENVIRONMENT AND HUMAN FACTORS   (Germany)

^f CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^g HUMBOLDT UNIVERSITY   (Germany)

Author keywords

Alternative testing; Cytotoxicity; Developing central nervous system; Hazard assessment; Neuronal development; Transcriptomics

Indexed keywords

4 CHLOROMERCURIBENZOIC ACID; BELINOSTAT; ENTINOSTAT; HISTONE DEACETYLASE INHIBITOR; MERCUROUS CHLORIDE; MERCURY DERIVATIVE; MERCURY(II)BROMIDE; METHYLMERCURY; ORGANOMERCURY COMPOUND; PANOBINOSTAT; PHENYLMERCURIC ACID; THIOMERSAL; TRANSCRIPTION FACTOR; TRANSCRIPTOME; TRICHOSTATIN A; UNCLASSIFIED DRUG; VALPROIC ACID; VORINOSTAT;

ARTICLE; AVIAN ERYTHROBLASTOSIS VIRUS E26 ONCOGENE; COAGULATION FACTOR II RECEPTOR LIKE 2 GENE; CONTROLLED STUDY; CYTOTOXIC CONCENTRATION; DEVELOPMENTAL TOXICITY; ENDOTHELIN RECEPTOR TYPE A GENE; FORKHEAD BOX D3 GENE; GENE; HAZARD ASSESSMENT; HOMEOBOX PROTEIN SIX3 GENE; HUMAN; HUMAN CELL; LIM HOMEOBOX 2 GENE; LONG TERM EXPOSURE; METALLOTHIONEIN 1E GENE; MICROARRAY ANALYSIS; NEUROECTODERM; NEUROTOXICITY; PLURIPOTENT STEM CELL; PREDICTION; PRIORITY JOURNAL; SUPPORT VECTOR MACHINE; TOXICITY TESTING; TRANSCRIPTION FACTOR AP 2 BETA GENE; TRANSCRIPTOMICS; VALIDATION STUDY; DNA MICROARRAY; DRUG EFFECTS; GENE EXPRESSION PROFILING; METABOLISM;

GENE EXPRESSION PROFILING; HISTONE DEACETYLASE INHIBITORS; HUMANS; NEURAL PLATE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; PLURIPOTENT STEM CELLS; TRANSCRIPTOME;

EID: 84940606580     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-015-1573-y     Document Type: Article

References (69)

1. Alexa ARJ (2010) topGO: enrichment analysis for gene ontology. R package 2.14.10. http://bioconductor.wustl.edu/bioc/html/topGO.html
2. Bahr GF, Moberger G (1954) Methyl-mercury-chloride as a specific reagent for protein-bound sulfhydryl groups; electron stains II. Exp Cell Res 6(2):506–518
3. Balmer NV, Leist M (2014) Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development. Basic Clin Pharmacol Toxicol 115(1):59–68
4. Balmer NV, Weng MK, Zimmer B et al (2012) Epigenetic changes and disturbed neural development in a human embryonic stem cell-based model relating to the fetal valproate syndrome. Hum Mol Genet 21(18):4104–4114
5. Balmer NV, Klima S, Rempel E et al (2014) From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol 88(7):1451–1468
6. Bal-Price AK, Coecke S, Costa L et al (2012) Advancing the science of developmental neurotoxicity (DNT): testing for better safety evaluation. ALTEX 29(2):202–215
7. Bal-Price A, Crofton KM, Leist M et al (2015) International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes. Arch Toxicol 89(2):269–287
8. Benjamini YH (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Stat Methodol 57:289–300
9. Cahan P, Li H, Morris SA, Lummertz da Rocha E, Daley GQ, Collins JJ (2014) Cell net: network biology applied to stem cell engineering. Cell 158(4):903–915
10. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27(3):275–280
11. Chen C, Grennan K, Badner J et al (2011) Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. PLoS ONE 6(2):e17238
12. Choi BH (1989) The effects of methylmercury on the developing brain. Prog Neurobiol 32(6):447–470
13. Colleoni S, Galli C, Gaspar JA et al (2011) Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci 124(2):370–377
14. Copp AJ, Greene ND, Murdoch JN (2003) The genetic basis of mammalian neurulation. Nat Rev Genet 4(10):784–793
15. Cortes CV (1995) Support-vector networks. Mach Learn 20:273–297
16. da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57
17. Efthymiou A, Shaltouki A, Steiner JP et al (2014) Functional screening assays with neurons generated from pluripotent stem cell-derived neural stem cells. J Biomol Screen 19(1):32–43
18. Ekino S, Susa M, Ninomiya T, Imamura K, Kitamura T (2007) Minamata disease revisited: an update on the acute and chronic manifestations of methyl mercury poisoning. J Neurol Sci 262(1–2):131–144
19. Falsig J, Porzgen P, Lund S, Schrattenholz A, Leist M (2006) The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function. J Neurochem 96(3):893–907
20. Fan J, Li R (2006) Statistical challenges with high dimensionality: feature selection in knowledge discovery. arXiv:math/0602133
21. Gerhardt E, Kugler S, Leist M et al (2001) Cascade of caspase activation in potassium-deprived cerebellar granule neurons: targets for treatment with peptide and protein inhibitors of apoptosis. Mol Cell Neurosci 17(4):717–731
22. Gocht T, Berggren E, Ahr HJ et al (2015) The SEURAT-1 approach towards animal free human safety assessment. ALTEX 32(1):9–24
23. Grandjean P, Herz KT (2011) Methylmercury and brain development: imprecision and underestimation of developmental neurotoxicity in humans. Mt Sinai J Med 78(1):107–118
24. Grinberg M, Stober RM, Edlund K et al (2014) Toxicogenomics directory of chemically exposed human hepatocytes. Arch Toxicol 88(12):2261–2287
25. Halsey YD (1955) The reaction of methyl mercury nitrate with the sulfhydryl groups of yeast glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem 214(2):589–593
26. Harada M (1995) Minamata disease: methylmercury poisoning in Japan caused by environmental pollution. Crit Rev Toxicol 25(1):1–24
27. Harbron C, Chang KM, South MC (2007) RefPlus: an R package extending the RMA algorithm. Bioinformatics 23(18):2493–2494
28. Harrill JA, Freudenrich TM, Machacek DW, Stice SL, Mundy WR (2011) Quantitative assessment of neurite outgrowth in human embryonic stem cell-derived hN2 cells using automated high-content image analysis. Neurotoxicology 31(3):277–290
29. Harris MJ, Juriloff DM (2007) Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects. Birth Defects Res A Clin Mol Teratol 79(3):187–210
30. Harris MJ, Juriloff DM (2010) An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. Birth Defects Res A Clin Mol Teratol 88(8):653–669
31. Hartung T, Leist M (2008) Food for thought… on the evolution of toxicology and the phasing out of animal testing. ALTEX 25(2):91–102
32. Ho Sui SJ, Fulton DL, Arenillas DJ, Kwon AT, Wasserman WW (2007) oPOSSUM: integrated tools for analysis of regulatory motif over-representation. Nucleic Acids Res 35(Web Server issue):W245–W252
33. Jagtap S, Meganathan K, Gaspar J et al (2011) Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol 162(8):1743–1756
34. Jergil M, Kultima K, Gustafson AL, Dencker L, Stigson M (2009) Valproic acid-induced deregulation in vitro of genes associated in vivo with neural tube defects. Toxicol Sci 108(1):132–148
35. Johnson WE, Li C, Rabinovic A (2007) Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics 8(1):118–127
36. Kadereit S, Zimmer B, van Thriel C, Hengstler JG, Leist M (2012) Compound selection for in vitro modeling of developmental neurotoxicity. Front Biosci 17:2442–2460
37. Khan N, Jeffers M, Kumar S et al (2008) Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J 409(2):581–589
38. Krug AK, Kolde R, Gaspar JA et al (2013) Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol 87(1):123–143
39. Kuegler PB, Zimmer B, Waldmann T et al (2010) Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing. ALTEX 27(1):17–42
40. Kultima K, Jergil M, Salter H, Gustafson AL, Dencker L, Stigson M (2010) Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenicity. Reprod Toxicol 30(3):457–468
41. Latta M, Kunstle G, Leist M, Wendel A (2000) Metabolic depletion of ATP by fructose inversely controls CD95- and tumor necrosis factor receptor 1-mediated hepatic apoptosis. J Exp Med 191(11):1975–1985
42. Leist M, Bremer S, Brundin P et al (2008a) The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy. ALTEX 25(3):163–190
43. Leist M, Hartung T, Nicotera P (2008b) The dawning of a new age of toxicology. ALTEX 25(2):103–114
44. Leist M, Hasiwa N, Rovida C et al (2014) Consensus report on the future of animal-free systemic toxicity testing. ALTEX 31(3):341–356
45. Meganathan K, Jagtap S, Wagh V et al (2012) Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells. PLoS ONE 7(8):e44228
46. Nau H, Hauck RS, Ehlers K (1991) Valproic acid-induced neural tube defects in mouse and human: aspects of chirality, alternative drug development, pharmacokinetics and possible mechanisms. Pharmacol Toxicol 69(5):310–321
47. Pallocca G, Fabbri M, Sacco MG et al (2013) miRNA expression profiling in a human stem cell-based model as a tool for developmental neurotoxicity testing. Cell Biol Toxicol 29(4):239–257
48. Pekkanen TJ, Sandholm M (1971) The effect of experimental methyl mercury poisoning on the number of sulfhydryl (SH) groups in the brain, liver and muscle of rat. Acta Vet Scand 12(4):551–559
49. Portales-Casamar E, Thongjuea S, Kwon AT et al (2010) JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res 38(Database issue):D105–D110
50. Rahnenfuhrer J, Leist M (2015) From smoking guns to footprints: mining for critical events of toxicity pathways in transcriptome data. Arch Toxicol 89(5):813–817
51. Robinson JF, Theunissen PT, van Dartel DA, Pennings JL, Faustman EM, Piersma AH (2011) Comparison of MeHg-induced toxicogenomic responses across in vivo and in vitro models used in developmental toxicology. Reprod Toxicol 32(2):180–188
52. Scherer A (2009) Batch effects and noise in microarray experiments: sources and solutions. Wiley, UK
53. Shinde V, Klima S, Sureshkumar PS et al (2015) Human pluripotent stem cell based developmental toxicity assays for chemical safety screening and systems biology data generation. J Vis Exp. doi:10.3791/52333(100)
54. Smirnova L, Block K, Sittka A, Oelgeschlager M, Seiler AE, Luch A (2014a) MicroRNA profiling as tool for in vitro developmental neurotoxicity testing: the case of sodium valproate. PLoS ONE 9(6):e98892
55. Smirnova L, Hogberg HT, Leist M, Hartung T (2014b) Developmental neurotoxicity—challenges in the 21st century and in vitro opportunities. ALTEX 31(2):129–156
56. Smyth GK, Michaud J, Scott HS (2005) Use of within-array replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21(9):2067–2075
57. Stiegler NV, Krug AK, Matt F, Leist M (2011) Assessment of chemical-induced impairment of human neurite outgrowth by multiparametric live cell imaging in high-density cultures. Toxicol Sci 121(1):73–87
58. Theunissen PT, Robinson JF, Pennings JL et al (2012) Transcriptomic concentration-response evaluation of valproic acid, cyproconazole, and hexaconazole in the neural embryonic stem cell test (ESTn). Toxicol Sci 125(2):430–438
59. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147
60. van Thriel C, Westerink RH, Beste C, Bale AS, Lein PJ, Leist M (2012) Translating neurobehavioural endpoints of developmental neurotoxicity tests into in vitro assays and readouts. Neurotoxicology 33(4):911–924
61. Volbracht C, Leist M, Nicotera P (1999) ATP controls neuronal apoptosis triggered by microtubule breakdown or potassium deprivation. Mol Med 5(7):477–489
62. Waldmann T, Rempel E, Balmer NV et al (2014) Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol 27(3):408–420
63. Weng MK, Zimmer B, Poltl D et al (2012) Extensive transcriptional regulation of chromatin modifiers during human neurodevelopment. PLoS ONE 7(5):e36708
64. Weng MK, Natarajan K, Scholz D et al (2014) Lineage-specific regulation of epigenetic modifier genes in human liver and brain. PLoS ONE 9(7):e102035
65. Werler MM, Ahrens KA, Bosco JL et al (2011) Use of antiepileptic medications in pregnancy in relation to risks of birth defects. Ann Epidemiol 21(11):842–850
66. Wheeler HE, Wing C, Delaney SM, Komatsu M, Dolan ME (2015) Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells. PLoS ONE 10(2):e0118020
67. Zimmer B, Kuegler PB, Baudis B et al (2011) Coordinated waves of gene expression during neuronal differentiation of embryonic stem cells as basis for novel approaches to developmental neurotoxicity testing. Cell Death Differ 18(3):383–395
68. Zimmer B, Lee G, Balmer NV et al (2012) Evaluation of developmental toxicants and signaling pathways in a functional test based on the migration of human neural crest cells. Environ Health Perspect 120(8):1116–1122
69. Zimmer B, Pallocca G, Dreser N et al (2014) Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery. Arch Toxicol 88(5):1109–1126