Fig. 1. Strategy for using iPS reprogramming to investigate iDILI.

Somatic cell samples such as skin or blood are collected from iDILI and control patients. These are used to derive hiPSCs that are exact genetic matches to the donor patients. Such hiPSCs can be indefinitely expanded and passaged, so long as they are maintained under pluripotent conditions. hiPSCs can then be differentiated to iHLCs (hepatocyte-like cells). iHLCs from iDILI and control patients can then be compared using functional tests (A., such as exposure to the iDILI-precipitating drug) or using transcriptome comparisons (B.), which may lead to identification of iDILI genes. Subsequently, causative mutations (C.) can be identified, using transcriptome alterations as a guide.