S2: Transcriptome changes
In vitro Toxicology and Biomedicine, University of Konstanz, Germany
Chair for in vitro Toxicology and Biomedicine
Analysis of transcriptome changes has become an established method to characterize the reaction of cells to toxicants and are increasingly accepted for in vitro alternative test methods. The qualitative analysis of transcriptome changes is well established but the challenge in toxicology is how to interpret, visualize such data in a quantitative manner to make them useful for risk assessment.
To address these issues we treated neurally differentiating human pluripotent stem cells with known neurodevelopmental teratogens (e.g. VPA, TSA, MeHg) and determined gene expression alterations based on whole transcriptome analysis. This biological test systems models early neural development and the cells differentiate to neuroectodermal progenitor cells. As a functional readout to phenotypically anchor the gene expression changes we further differentiate these cells to the so called neural rosettes stage, which may correlate to neural tube closure in vivo. Using this test system, we performed extensive concentration response and time window analysis. Further, we used various visualization and pathway enrichment tools to describe the cellular responses that occur with different concentrations and developmental stages.