In this study, a novel culture system for the differentiation of human embryonic stem cell aggregates is described, and its utility for teratogenicity assessment is evaluated. Culture conditions were optimized and resulted in 3-dimensional aggregates that exhibit characteristics of the axial skeleton and central nervous system precursors.
To examine the impact of teratogenic exposures on the differentiation, 18 compounds were tested, for which adequate information on in vivo plasma concentrations is available. Aggregates treated with each compound were examined for gross morphology and on transcript levels of 15 embryogenesis regulator genes via RNA sequencing. Significant alterations in the transcript levels were observed for 94% of the teratogenic exposures, whereas no alteration was observed for 92% of the non-teratogenic exposures.
The results demonstrate that transcriptional changes in embryonic stem cell aggregates can serve as a predictive indicator of teratogenicity.
Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells
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