Chapter 8: Epigenetic Impact of Stem Cell Toxicants

Human embryonic stem cells (ESCs) virtually represent the simulation source of a wide range of modern tissue specific toxicity models with an ability to replace the conventional animal models. Dynamic landscapes of epigenetic alterations play an essential role in regulation of multi-lineage differentiation capabilities and other relevant attributes of ESCs. Exogenous agents that are able to interfere with such programming may act as developmental toxicants. These stem cell toxicants have been reported to either induce or respond to complex biological signaling cascades including epigenetic perturbations. Herein, we propose that chemical toxicant-induced epigenetic changes of stem cells in the form of promoter DNA/histone methylation at a few repressed genes could poise their cellular phenotype. This may cause either abnormal expansion of their number or inhibition of their differentiation ability. In this chapter, we will discuss the biochemical characteristics and epigenetic effects of various stem cell toxicants. We will also cover the possibilities for incorporation of epigenetic assays in stem cell toxicological studies.