Pluripotent stem cells (PSCs) undergo dynamic changes as they differentiate and eventually give rise to all somatic and germ cell lineages of a developing embryo. In the late epiblast stage following implantation, PSCs ‘primed’ for differentiation are called epiblast stem cells (EpiSCs), in contrast to ground-state naïve PSCs. Although PSC transcriptional profiles are well characterised, how cell architecture and mechanics change in different pluripotent states is underexplored. In this study (Liu et al., 2025), Pakorn Kanchanawong and colleagues employ structured illumination super-resolution microscopy to investigate the nuances of actin cytoskeletal architecture between ground-state mouse embryonic stem cells (mESCs) and EpiSCs. In ground-state mESCs, the authors discover novel actin- and cadherin-enriched structures in the cell cortex, termed non-junctional cadherin complexes (NJCCs), as they are not associated with cell–cell junctions despite containing proteins typically associated with adherens junctions. NJCCs, which are dependent on cadherin extracellular domains and low levels of the Rho GTPase Rac1, disappear in EpiSCs, suggesting a potential function in maintaining ground-state pluripotency. As previous studies have correlated key mechanical properties of PSCs at different stages of embryonic development with other distinct actin-based structures, the identification of NJCCs contributes to our growing understanding of how the cytoskeleton regulates and responds to changes in pluripotent state.
