Human induced pluripotent stem cells (iPSC) offer a perspective of unlimited supply of cells to be used for animal-free studies of toxicity. Therefore, research into the mechanisms by which specific cellular fates, such as those of hepatic and neuronal cell lineages, can be adopted by iPSC is rapidly expanding. However, current protocols for the generation of iPSC-derived cells suffer from poor establishment of cellular identity.
The research group demonstrated that current methods mimicking developmental signaling processes in vitro to derive hepatocyte-like cells (HLC) from iPSC fail to induce complete commitment to the hepatocyte lineage. Rather, HLC differentiation produces cells with features from hepatocytes, intestinal and other cell types together in one ‘hybrid cell’.
The team approaches these challenges by applying state of the art molecular biology techniques in combination with bioinformatics to analyze and alter the transcriptomic and epigenetic state of iPSC-derived cells. Central goals include identification and activation of gene regulatory networks that promote correct differentiation but are inactive in iPSC-derived cells as well as identification and suppression of gene regulatory networks that promote hybrid state differentiation.
Although there are remaining challenges, iPSC technology offers the unique possibility to study the effect of developmental toxicants on cell differentiation. Therefore, the researchers are establishing an iPSC-based in vitrotest system for the assessment of developmental toxicity in neuronal progenitor cells. The research is conducted in close cooperation with project groups in the Department of Toxicology and the Department of Immunology as well as national and international partners.