title: Auxetic nuclei in embryonic stem cells exiting pluripotency.
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. Here, we show that during the transition, the nuclei of ESCs are auxetic: they exhibit a cross-sectional expansion when stretched and a cross-sectional contraction when compressed, and their stiffness increases under compression. We also show that the auxetic phenotype of transition ESC nuclei is driven at least in part by global chromatin decondensation. Through the regulation of molecular turnover in the differentiating nucleus by external forces, auxeticity could be a key element in mechanotransduction. Our findings highlight the importance of nuclear structure in the regulation of differentiation and reprogramming.
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pagliara
authors.affiliation: Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge, CB2 3DY, UK.
authors.forename: Kristian
authors.initials: K
authors.lastname: Franze
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.|Wellcome Trust/Medical Research Council Cambridge Stem Cell Research Institute and Madingley Road, University of Cambridge, Cambridge, CB3 0ES, UK.
authors.forename: Crystal R
authors.initials: CR
authors.lastname: McClain
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.
authors.forename: George
authors.initials: G
authors.lastname: Wylde
authors.affiliation: Wellcome Trust/Medical Research Council Cambridge Stem Cell Research Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QR, UK.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Fisher
authors.affiliation: Wellcome Trust/Medical Research Council Cambridge Stem Cell Research Institute and Madingley Road, University of Cambridge, Cambridge, CB3 0ES, UK.
authors.forename: Robin J M
authors.initials: RJM
authors.lastname: Franklin
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge, CB2 1PZ, UK.
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Kabla
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Keyser
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, CB3 0HE, UK.|Wellcome Trust/Medical Research Council Cambridge Stem Cell Research Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QR, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Chalut
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*
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