Plakoglobin is a mechanoresponsive regulator of naïve pluripotency

Abstract

Biomechanical cues are instrumental in guiding embryonic development and cell differentiation. Understanding how these physical stimuli translate into transcriptional programs could provide insight into mechanisms underlying mammalian pre implantation development. Here, we explore this by exerting microenvironmental control over mouse embryonic stem cells (ESCs). Microfluidic encapsulation of ESCs in agarose microgels stabilized the naïve pluripotency network and specifically induced expression of Plakoglobin (Jup), a vertebrate homologue of β-catenin. Indeed, overexpression of Plakoglobin was sufficient to fully re establish the naïve pluripotency gene regulatory network under metastable pluripotency conditions, as confirmed by single cell transcriptome profiling. Finally, we found that in the epiblast, Plakoglobin was exclusively expressed at the blastocyst stage in human and mouse embryos — further strengthening the link between Plakoglobin and naïve pluripotency in vivo. Our work reveals Plakoglobin as a mechanosensitive regulator of naïve pluripotency and provides a paradigm to interrogate the effects of volumetric confinement on cell fate transitions.

Meeting report: Third Franco‐Japanese developmental biology meeting “New Frontiers in developmental biology: Celebrating the diversity of life”

“…The sixth session was "Dynamics processes, imaging advances and new models in developmental biology." In this session, six speakers showed dynamics of developmental process using novel imaging tools or novel techniques such as cell spatial confinement using droplet microfluidics (Kohler et al, 2022) Discontinuities (bursting) and heterogeneities seems to be the rule for these processes (Dufourt et al, 2021;Pimmett et al, 2021). Yoshikatsu Sato (Nagoya University) presented an application of microfluidics in the field of plant development which enabled to demonstrate the developmental flexibility of tip-growth.…”