Transcriptional Networks Regulating Embryonic Stem Cell Fate Decisions

Abstract

A comprehensive understanding of the transcrip-tional regulation of embryonic stem cell (ESC) fate decisions will provide the key to their successful manipulation for ther-apeutic purposes as well as provide insight into the process of early embryogenesis. Traditional molecular and genetic approaches have been successful in identifying several es-sential regulators of pluripotency, notably Oct4, Nanog, and Sox2. However, these approaches will not be sufficient to understand the global regulatory control of transcriptional networks. Genome-wide work in model organisms such as Escherichia coli, yeast, and sea urchin reveal that transcrip-tional networks can be broken down into a small set of evolutionarily conserved network motifs, each with its own biological function. Initial genome-wide studies in ESCs re-veal the presence of these same network motifs, providing mechanistic explanations of cell fate decisions. Thus, as is being performed in lower organisms, the drafting of a com-prehensive transcriptional network controlling ESC fate will require systematic characterisation of the functional targets of each ESC-expressed transcription factor.