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The directed differentiation of human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) into hepatocytes could facilitate a rational study of the molecular mechanisms underlying human liver development as well as provide a renewable source of exogenous hepatocytes for drug toxicity testing and cell-based therapeutics. Moreover, if hepatocytes were produced from hiPSCs originating from patients with inborn errors of hepatic metabolism, such cells could be used for modeling liver disease.

The pluripotency of embryonic stem (ES) cells is the result of a highly dynamic equilibrium that is controlled by a complex network of transcription factors that confer unique transcriptional properties to ES cells. Regulation of gene expression appears to correlate with the presence of dual chromatin marks called bivalent domains at the promoters of poised developmental genes. These marks keep differentiation genes silenced but poised and ready to be activated or permanently repressed during differentiation.