Comparison of gene expression regulation in mouse- and human embryonic stem cell assays during neural differentiation and in response to valproic acid exposure

被引:6
作者
Schulpen, Sjors H. W. [1 ,2 ]
Theunissen, Peter T. [1 ]
Pennings, Jeroen L. A. [1 ]
Piersma, Aldert H. [1 ,2 ]
机构
[1] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect, Bilthoven, Netherlands
[2] Univ Utrecht, Fac Vet Med, Inst Risk Assessment Sci, Utrecht, Netherlands
关键词
Embryonic stem cells; Transcriptomics; Developmental neuro toxicity; Valproic acid; Neural differentiation; DEVELOPMENTAL TOXICITY; NEURONAL DIFFERENTIATION; CARDIOMYOCYTES; MESODERM; TERATOGENICITY; PROLIFERATION; NEUROTOXICITY; NORMALIZATION; MUTATIONS; MIGRATION;
D O I
10.1016/j.reprotox.2015.06.043
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Embryonic stem cell tests (EST) are considered promising alternative assays for developmental toxicity testing. Classical mouse derived assays (mEST) are being replaced by human derived assays (hEST), in view of their relevance for human hazard assessment. We have compared mouse and human neural ESTn assays for neurodevelopmental toxicity as to regulation of gene expression during cell differentiation in both assays. Commonalities were observed in a range of neurodevelopmental genes and gene ontology (GO) terms. The mESTn showed a higher specificity in neurodevelopment than the hESTn, which may in part be caused by necessary differences in test protocols. Moreover, gene expression responses to the anticonvulsant and human teratogen valproic acid were compared. Both assays detected pharmacological and neurodevelopmental gene sets regulated by valproic acid. Common significant expression changes were observed in a subset of homologous neurodevelopmental genes. We suggest that these genes and related GO terms may provide good candidates for robust biomarkers of neurodevelopmental toxicity in hESTn. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:77 / 86
页数:10
相关论文
共 86 条
[11]   T-profiler: scoring the activity of predefined groups of genes using gene expression data [J].
Boorsma, A ;
Foat, BC ;
Vis, D ;
Klis, F ;
Bussemaker, HJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 :W592-W595
[12]   Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects [J].
Bosoi, Ciprian M. ;
Capra, Valeria ;
Allache, Redouane ;
Vincent Quoc-Huy Trinh ;
De Marco, Patrizia ;
Merello, Elisa ;
Drapeau, Pierre ;
Bassuk, Alexander G. ;
Kibar, Zoha .
HUMAN MUTATION, 2011, 32 (12) :1371-1375
[13]   Valproic acid in normal therapeutic concentration has no neuroprotective or differentiation influencing effects on long term expanded murine neural stem cells [J].
Brunn, Judith ;
Wiroth, Viktor ;
Kowalski, Michael ;
Runge, Uwe ;
Sabolek, Michael .
EPILEPSY RESEARCH, 2014, 108 (04) :623-633
[14]   A Human Stem Cell-Based Model for Identifying Adverse Effects of Organic and Inorganic Chemicals on the Developing Nervous System [J].
Buzanska, Leonora ;
Sypecka, Joanna ;
Nerini-Molteni, Silvia ;
Compagnoni, Anna ;
Hogberg, Helena T. ;
del Torchio, Riccardo ;
Domanska-Janik, Krystyna ;
Zimmer, Jens ;
Coecke, Sandra .
STEM CELLS, 2009, 27 (10) :2591-2601
[15]   Dimerization of the EphA1 Receptor Tyrosine Kinase Transmembrane Domain: Insights into the Mechanism of Receptor Activation [J].
Chavent, Matthieu ;
Chetwynd, Alan P. ;
Stansfeld, Phillip J. ;
Sansom, Mark S. P. .
BIOCHEMISTRY, 2014, 53 (42) :6641-6652
[16]   Development of a Neural Teratogenicity Test Based on Human Embryonic Stem Cells: Response to Retinoic Acid Exposure [J].
Colleoni, Silvia ;
Galli, Cesare ;
Gaspar, John Antony ;
Meganathan, Kesavan ;
Jagtap, Smita ;
Hescheler, Jurgen ;
Sachinidis, Agapios ;
Lazzari, Giovanna .
TOXICOLOGICAL SCIENCES, 2011, 124 (02) :370-377
[17]   A NOVEL POU HOMEODOMAIN GENE SPECIFICALLY EXPRESSED IN CELLS OF THE DEVELOPING MAMMALIAN NERVOUS-SYSTEM [J].
COLLUM, RG ;
FISHER, PE ;
DATTA, M ;
MELLIS, S ;
THIELE, C ;
HUEBNER, K ;
CROCE, CM ;
ISRAEL, MA ;
THEIL, T ;
MOROY, T ;
DEPINHO, R ;
ALT, FW .
NUCLEIC ACIDS RESEARCH, 1992, 20 (18) :4919-4925
[18]   Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data [J].
Dai, MH ;
Wang, PL ;
Boyd, AD ;
Kostov, G ;
Athey, B ;
Jones, EG ;
Bunney, WE ;
Myers, RM ;
Speed, TP ;
Akil, H ;
Watson, SJ ;
Meng, F .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e175.1-e175.9
[19]   Osteoblast differentiation of murine embryonic stem cells as a model to study the embryotoxic effect of compounds [J].
de Jong, Esther ;
van Beek, Lianne ;
Piersma, Aldert H. .
TOXICOLOGY IN VITRO, 2012, 26 (06) :970-978
[20]  
De kock J, 2012, ALTEX, V1, P541