Role of retinoic acid in the differentiation of embryonal carcinoma and embryonic stem cells.

Retinoic acid (RA), the most potent natural form of vitamin A, plays an important role in many diverse biological processes such as embryogenesis and cellular differentiation. This chapter is a review of the mechanism of action of RA and the role of specific RA-regulated genes during the cellular differentiation of embryonal carcinoma (EC) and embryonic stem (ES) cells. RA acts by binding to its nuclear receptors and inducing transcription of specific target genes. The most studied mouse EC cell lines include F9 cells, which can be induced by RA to differentiate into primitive, parietal, and visceral endodermal cells; and P19 cells, which can differentiate to endodermal and neuronal cells upon RA treatment. ES cells can be induced to differentiate into a number of different cell types; many of which require RA treatment. Over the years, many RA-regulated genes have been discovered in EC and ES cells using a diverse set of techniques. Current research focuses on the elucidation how these genes affect differentiation in EC and ES cells using a variety of molecular biology approaches. However, the exact molecule events that lead from a pluripotent stem cell to a fully differentiated cell following RA treatment are yet to be determined.