Postdoctoral Research Associate University of Cambridge Cambridge, United Kingdom
Abstract: Biomechanical cues are instrumental in guiding embryonic development and cell differentiation. Understanding how physical stimuli regulate transcriptional programs provides key insights into mechanisms underlying mammalian pre-implantation development and pluripotency transitions. We explore this regulation using a microfluidic platform to encapsulate mouse embryonic stem cells in agarose microgels, exerting precise microenvironmental control. This approach stabilizes the naive pluripotency network and specifically induces the expression of Plakoglobin (Jup), a vertebrate homolog of β-catenin and potential modulator of WNT/β-catenin signaling.
Overexpression of Plakoglobin re-establishes the naive pluripotency gene regulatory network under metastable conditions, as confirmed by single-cell transcriptome profiling. Finally, we find that, in the epiblast, Plakoglobin was exclusively expressed at the blastocyst stage in human and mouse embryos – further strengthening the link between Plakoglobin and naive pluripotency in vivo.
Our findings reveal Plakoglobin as a pivotal mediator of the interplay between biomechanical signals and transcriptional regulation, offering new perspectives on WNT pathway dynamics and cell-fate decisions during early embryogenesis.
