Abstract
Despite our current understanding of transcriptional and epigenetic programs regulating transitions of human embryonic stem cells between distinct stages of pluripotency1,2, our knowledge of morphological changes in pluripotency states remains limited. We report remodeling of the actin cytoskeleton of human embryonic stem cells (hESCs) as they transition from primed to naïve pluripotency, which includes assembly of a supracellular ring of contractile actin filaments encapsulating colonies of naïve hESCs. Formation of the actin ring requires activity of the Arp2/3 complex, which promotes uniform cell mechanics within naïve colonies. Arp2/3 complex activity is also necessary for effective transition to naïve pluripotency, through regulation of Hippo signaling and translocation of the Hippo pathway effectors YAP and TAZ from the cytosol to the nucleus. In hESCs with inhibited Arp2/3 complex activity, expression of a constitutively active, nuclear-localized YAP-S127A rescues the naïve pluripotent state, including established markers and colony formation. Together our findings on the cell biology of hESCs reveal a new mechanism by which cytoskeletal dynamics can coordinate cell mechanics to change gene expression and facilitate transitions between pluripotency states.
Competing Interest Statement
The authors have declared no competing interest.