Background: Human embryonic stem cells (hESCs) partially recapitulate early embryonic three germ layer\ndevelopment, allowing testing of potential teratogenic hazards. Because use of hESCs is ethically debated, we\ninvestigated the potential for human induced pluripotent stem cells (hiPSCs) to replace hESCs in such tests.\nMethods: Three cell lines, comprising hiPSCs (foreskin and IMR90) and hESCs (H9) were differentiated for 14 days.\nTheir transcriptome profiles were obtained on day 0 and day 14 and analyzed by comprehensive bioinformatics tools.\nResults: The transcriptomes on day 14 showed that more than 70% of the ââ?¬Å?developmental genesââ?¬Â (regulated genes\nwith > 2-fold change on day 14 compared to day 0) exhibited variability among cell lines. The developmental genes\nbelonging to all three cell lines captured biological processes and KEGG pathways related to all three germ layer\nembryonic development. In addition, transcriptome profiles were obtained after 14 days of exposure to teratogenic\nvalproic acid (VPA) during differentiation. Although the differentially regulated genes between treated and untreated\nsamples showed more than 90% variability among cell lines, VPA clearly antagonized the expression of developmental\ngenes in all cell lines: suppressing upregulated developmental genes, while inducing downregulated ones. To quantify\nVPA-disturbed development based on developmental genes, we estimated the ââ?¬Å?developmental potencyââ?¬Â (Dp) and\nââ?¬Å?developmental indexââ?¬Â (Di).\nConclusions: Despite differences in genes deregulated by VPA, uniform Di values were obtained for all three cell lines.\nGiven that the Di values for VPA were similar for hESCs and hiPSCs, Di can be used for robust hazard identification,\nirrespective of whether hESCs or hiPSCs are used in the test systems.
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