Abstract

Embryonic stem cells (ESCs) self-renew in a state of naïve pluripotency, in which they are competent to generate all somatic cells. It has been hypothesized that, before irreversibly committing, ESCs pass through at least one metastable transition state. This transition would represent a gateway for differentiation and reprogramming of somatic cells. We sought a mechanical phenotype of transition by probing the nuclear response to compressive and tensile forces and found that, only during transition, nuclei of ESCs are auxetic: they displayed a cross-sectional expansion when stretched and a cross-sectional contraction when compressed, and their stiffness increased under compression. We showed recently that the auxetic phenotype of transition ESC nuclei is driven at least in part by global chromatin decondensation. Our findings highlight the importance of nuclear structure in the regulation of differentiation and reprogramming. Importantly, there are also significant volume implications we explored for the auxetic phenotype in ESC nuclei during transition. Stretched auxetic nuclei expand significantly in volume, whilst compressed auxetic nuclei condense significantly in volume; this is very unlike most materials, which tend to conserve or lose volume under stress. Therefore, I will discuss how the physical properties of these nuclei in a dynamically remodeling tissue could enhance differentiative capacity by acting as stress-driven auxetic pumps to increase molecular turnover.