Teratogen screening using transcriptome profiling of differentiating human embryonic stem cells.
Bottom Line: To examine teratogenic effects on early human development we performed non-biased expression profiling of differentiating human embryonic and induced pluripotent stem cells treated with several drugs--ethanol, lithium, retinoic acid (RA), caffeine and thalidomide, which is known to be highly species specific.Our results point to the potency of specific teratogens and their affected tissues and pathways.Specifically, we could show that ethanol caused dramatic increase in endodermal differentiation, RA caused misregulation of neural development and thalidomide affected both these processes.
Affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.Show MeSH
Related in: MedlinePlus
Mentions: In this study we treated developing EBs for 7 days with various teratogens at concentrations corresponding to documented human serum levels [8, 22]. Caffeine as a negative control was used at a concentration shown to induce malformations in mice . Following treatment, gene expression was analysed using DNA microarrays. Expression results were analysed relative to their respective untreated controls and genes whose expression was significantly changed (over 2-fold) were counted. Lithium, caffeine and 0.5% ethanol produced little or no effect. Higher doses of ethanol (1.5% and 2%), RA and thalidomide had more dramatic effects with several hundred probesets changing in their levels of expression (Fig. 1A).
Affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.