Pluripotent stem cells (PSCs) are a promising source of material for various cell-based therapies and vital for the understanding of early human development. Maintenance of PSCs and creation of various somatic cell types is orchestrated by the integrations of very complex networks and understanding how their cell-cycle is regulated can improve their maintenance and differentiation in vitro. Here I demonstrated, with the utilization of the FUCCI reporter system, a novel signaling event occurring in the G1 phase of human embryonic stem cells (hESCs). MicroRNAs are major regulators of self-renewal and differentiation in hESCs, allowing for broad and rapid changes in their transcriptional profiles. I identified a microRNA located within a primate-specific microRNA cluster, miR-520g, which regulates the inhibitory Smad6. I also show Smad6 being necessary for mesoderm commitment, which reveals a novel role of Smad6 outside of its autoinhibitory activity in Activin/TGF signaling.