Differentiation of an embryonic stem cell (ESC) requires both suppression of self-renewal and activation of a specific differentiation pathway. The small non-coding RNAs known as microRNAs (miRNAs) are emerging as important players in the orchestration of cell fate. Now the prominent miRNA, let-7, is shown to be responsible for suppressing the self-renewal program in ESCs. This inhibition can be reversed by a family of ESC-regulating (ESCC) miRNAs that regulate the cell cycle, suggesting that the interplay between let-7 and ESCC miRNAs provides a mechanism capable of dictating cell fate. Full story