Arp2/3 complex activity enables nuclear YAP for naïve pluripotency of human embryonic stem cells
Year: 2024
Type: article
Abstract: Our understanding of the transitions of human embryonic stem cells (hESCs) between distinct stages of pluripotency relies predominantly on regulation by transcriptional and epigenetic programs with limited insight on the role of established morphological changes. We report remodeling of the actin cytoskeleton of hESCs as they transition from primed to naïve pluripotency which includes assembly of a ring of contractile actin filaments encapsulating colonies of naïve hESCs. Activity of the Arp2/3 complex is required for formation of the actin ring, to establish uniform cell mechanics within naïve colonies, to promote nuclear translocation of the Hippo pathway effectors YAP and TAZ, and for effective transition to naïve pluripotency. RNA-sequencing analysis confirms that Arp2/3 complex activity regulates Hippo signaling in hESCs, and impaired naïve pluripotency with inhibited Arp2/3 complex activity is rescued by expressing a constitutively active, nuclear-localized YAP-S127A. Moreover, expression of YAP-S127A partially restores the actin filament fence with Arp2/3 complex inhibition, suggesting that actin filament remodeling is both upstream and downstream of YAP activity. These new findings on the cell biology of hESCs reveal a mechanism for cytoskeletal dynamics coordinating cell mechanics to regulate gene expression and facilitate transitions between pluripotency states.
Source: eLife
DOI: 10.7554/elife.89725
Authors: Nathaniel P. Meyer, Tania Singh, Matthew L. Kutys, Todd Nystul, Diane L. Barber
Institution: University of California, San Francisco
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, National Institutes of Health, University of California, San Francisco, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Origins and Biological Consequences of Human Infertility, The role of intracellular pH in the specification of cell fate, Shear stress-mediated Notch1 activation by intrinsic cell adhesive and cytoskeletal activity, Center for Research, Innovation and Training in Reproduction and Infertility, G7199678765, Wide-field super-resolution spinning disk confocal microscope, G7266965569, G743387500, Predoctoral Training in Developmental Biology, Decoding cortical Notch signaling and morphogenic instruction at cell-cell interfaces, Cell Fate Decisions in Epithelial Stem Cell Lineages
OpenAlex ID: W4402849858