Establishment of a Human iPSC Reporter-Based Developmental Toxicity Assay that Detects FGF Signal Disruption
The number of man-made chemicals has increased exponentially in recent decades, and some of them induce fetal malformations. Because complex and precisely programmed signaling pathways play important roles in developmental processes, their disruption by external chemicals often triggers developmental toxicity. However, highly accurate and high-throughput screening assays for potential developmental toxicants are currently lacking. In this study, we propose a reporter assay that utilizes human induced pluripotent stem cells (iPSCs) to detect changes in fibroblast growth factor signaling, which is essential for limb morphogenesis. The dynamics of this signaling after an exposure to a chemical were integrated to estimate the degree of signaling disruption, which afforded a good prediction of the capacity of chemicals listed in the ECVAM International Validation Study that induce limb malformations. This is our initial report about a human iPSC-based signaling disruption assay, which could be useful for the screening of potential developmental toxicants.