Global transcriptional profiling of time dependent multilineage differentiation of human embryonic stem cells and its implications for developmental toxicity assessments

Kesavan Meganathan, Smita Jagtap, Vilas Wagh, John Gaspar, Jürgen Hescheler and Agapios Sachinidis, Institute of Neurophzsiology, University of Köln, Germany

The better understanding of early human embryonic development has been hampered with the availability of samples and eventually addressed with in vivo embryonic development (ED). To study evolutionarily conserved, developmentally regulated pathways and genes for toxicity analysis, in vivo studies were extrapolated. As an initial step we have recapitulated the early human ED with multilineage differentiation of human embryonic stem cells (hESC) integrated with sensitive genomics approach in our prior publication. To further explore the human ED and its subsequent application in toxicogenomics we have assigned the time kinetic hESC ED assays. The global transcriptional profiling and the subsequent gene ontology analysis reveal that from day 3 the developmental biological processes were identified. Also, the gene signatures identified during the embryonic development were used for the assessment of early developmental toxicity. The known developmental toxicants and the negative compound were treated at sub lethal concentration during the Embryoid body development for 14 days. The gene expression analysis for the toxicity markers were measured with RT-qPCR and reveal these positive compounds have distinctive effect on mRNA level for these markers (AFP, DCN, APOA2, IGFBP3, HAND1, POSTN, PITX2, COL3A1 and MSX1) but the negative compound penicillin doesn’t show any significant effect.