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Dgcr8 knockout embryonic stem cells (ESCs) proliferate at a slower rate with a slight accumulation of cells in G1 phase, and cannot silence the self-renewal when induced to differentiate, suggesting miRNAs as important regulators of ESC self-renewal and differentiation.Introduction of miR-294/302 family of miRNAs, the most highly enriched miRNAs in ESCS, to Dgcr8 knockout ESCs promotes proliferation and reverses the accumulation of cells in G1 phase.In contrast, introduction of somatic cell enriched let-7 family and several lineage-specific miRNAs silence the self-renewal of Dgcr8 knockout ESCs.Interestingly, miR294/302 family can prevent the silencing of self-renewal by let-7 and the other differentiation inducing miRNAs.These data establishes miR-294/302 family as a central player in regulating ESC cell cycle and self-renewal.Here we report our recent progress on understanding the working mechanism of this important family of miRNAs.