MicroRNA Regulation of Embryonic Stem Cell Self-Renewal and Differentiation.

Stem cell differentiation requires a complex coordination of events to transition from a self-renewing to a differentiated cell fate. Stem cells can be pluripotent (capable of giving rise to all embryonic lineages), multipotent (possessing the potential to give rise to multiple lineages) and unipotent (capable of given rise to a single cell lineage). Regardless of their potency all stem cells must silence their self-renewal program during differentiation. The self-renewal program can be defined as the integration of external and internal stimuli that enables a cell to proliferate while maintaining its potency. Two hallmarks of the self-renewal program are a self-reinforcing transcriptional network and a specialized cell-cycle profile. In this chapter we discuss the impact of various microRNAs (miRNAs) to either reinforce or inhibit the self-renewal program of stem cells and how this added regulatory layer provides robustness to cell-fate decisions. We will focus on embryonic stem cells (ESCs) describing miRNA function in self-renewal, differentiation and de-differentiation. We will compare and contrast miRNA functions in ESCs with miRNA function in lineage specific somatic stem cells and in cancer.