ArticleBritish journal of pharmacology2011
Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation.
Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 41 citations in OpenAlex.
- Pluripotent stem cell assays: Modalities and applications for predictive developmental toxicity.Current research in toxicology · 2022Article
- A novel human pluripotent stem cell-based assay to predict developmental toxicity.Archives of toxicology · 2020Article
- Expression of Fibroblast Growth Factor 4 in a Rat Model of Polydactyly of the Thumb Induced by Cytarabine.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- CALISTA: Clustering and LINEAGE Inference in Single-Cell Transcriptional Analysis.Frontiers in bioengineering and biotechnology · 2020Article
- Teratogen screening with human pluripotent stem cells.Integrative biology : quantitative biosciences from nano to macro · 2018Review
- Pluripotent Stem Cells in Developmental Toxicity Testing: A Review of Methodological Advances.Toxicological sciences : an official journal of the Society of Toxicology · 2018Review
- Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-ToxArchives of toxicology · 2017Article
- Article
- Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene.Scientific reports · 2016Article
- Gene-modified embryonic stem cell test to characterize chemical risks.Environmental science and pollution research international · 2015Article
- A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors.Archives of toxicology · 2015Article
- Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.Journal of visualized experiments : JoVE · 2015Article
- Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells.Cell death & disease · 2015Article
- Profiling of drugs and environmental chemicals for functional impairment of neural crest migration in a novel stem cell-based test battery.Archives of toxicology · 2014Article
- Assessment of Developmental Toxicants using Human Embryonic Stem Cells.Toxicological research · 2013Review
- Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach.Archives of toxicology · 2013Article
- Identification of thalidomide-specific transcriptomics and proteomics signatures during differentiation of human embryonic stem cells.PloS one · 2012Article
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7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeTeratogenic substances induce adverse effects during the development of the embryo. Multilineage differentiation of human embryonic stem cells (hESCs) mimics the development of the embryo in vitro. Here, we propose a transcriptomic approach in hESCs for monitoring specific toxic effects of compounds as an alternative to traditional time-consuming and cost-intensive in vivo tests requiring large numbers of animals. This study was undertaken to explore the adverse effects of cytosine arabinoside (Ara-C) on randomly differentiated hESCs. EXPERIMENTAL APPROACH: Human embryonic stem cells were used to investigate the effects of a developmental toxicant Ara-C. Sublethal concentrations of Ara-C were given for two time points, day 7 and day 14 during the differentiation. Gene expression was assessed with microarrays to determine the dysregulated transcripts in presence of Ara-C. KEY
resultsRandomly differentiated hESCs were able to generate the multilineage markers. The low concentration of Ara-C (1 nM) induced the ectoderm and inhibited the mesoderm at day 14. The induction of ectodermal markers such as MAP2, TUBB III, PAX6, TH and NESTIN was observed with an inhibition of mesodermal markers such as HAND2, PITX2, GATA5, MYL4, TNNT2, COL1A1 and COL1A2. In addition, no induction of apoptosis was observed. Gene ontology revealed unique dysregulated biological process related to neuronal differentiation and mesoderm development. Pathway analysis showed the axon guidance pathway to be dysregulated. CONCLUSIONS AND IMPLICATIONS: Our results suggest that hESCs in combination with toxicogenomics offer a sensitive in vitro developmental toxicity model as an alternative to traditional animal experiments.
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