Arp2/3 Complex Activity Enables Nuclear YAP for Naïve Pluripotency of Human Embryonic Stem Cells

Despite current understanding of transcriptional and epigenetic programs regulating transitions of human embryonic stem cells between distinct stages of pluripotency, our knowledge of the cell biology of changes in pluripotency states remains limited. We report a dynamic remodeling of the actin cytoskeleton of human embryonic stem cells (hESCs) as they transition from primed to naïve pluripotency that includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. The actin ring requires activity of the Arp2/3 complex and traction force microscopy suggests a role in limiting cell-substrate tensional forces. Arp2/3 complex activity is also necessary for effective transition to the naïve pluripotency state, including translocation of the Hippo pathway effectors YAP and TAZ from the cytosol to the nucleus. In hESCs with inhibited Arp2/3 complex activity, expressing a nuclear-localized YAP-S127A restores assembly of the actin ring and the naïve pluripotency state, including established markers and colony formation. Together these new findings on the cell biology of hESC reveal a signaling network of Arp2/3 complex activity for dynamic remodeling of contractile actin filaments and YAP/TAZ activity for transition to the naïve pluripotency state.