Embryonic stem (ES) cells possess unique therapeutic potential due to their ability to give rise to all the cells of the body. One of the major focuses of stem cell research is to develop in vitro differentiation protocols that result in highly enriched populations of the desired cell type. These differentiated cells could potentially be used for replacement cell therapy, disease modeling or drug screening.

Currently many differentiation strategies are inefficient with only a small number of cells being successfully converted to the desired cell lineage. Understanding the molecular events regulating the differentiation of ES cells to specific cell types is critical if their therapeutic potential is to be realized. At the heart of differentiation lie two major events; proliferation and changes in gene expression. Regulation of gene expression can occur in a variety of ways and ultimately determines the fate of the differentiating cell.

Genes are transcribed into mRNAs which are then further translated into protein, the functional unit. ES cells have to implement very specific patterns of protein expression to enable differentiation into different cell types. This is a tightly orchestrated process that ensures the correct proteins are produced only at the required developmental stages. During differentiation, cells proceed down a differentiation pathway that is driven by constant changes in the proteins that are being expressed in that cell. This enables cells to transition from an ES cell to a fully differentiated cell in a coordinated manner.

The major point of regulation of gene expression is transcription and when ES cells differentiate there is a dramatic reorganization of the transcriptome in the cell. Significant work has focused on deciphering the transcriptional networks that regulate self-renewal and differentiation and the roles of individual transcription factors have been described in promoting maintenance of the ES cell state or directing lineage specific differentiation.

While transcription is the major driver of differentiation, many other controls exist to regulate and promote differentiation and self renewal. It is the post-transcriptional controls that really determine the final rate of protein production. Production of proteins is regulated at the level of translation and recent work has begun to elucidate the translational controls operating during ESC differentiation.