The self-renewal of mouse embryonic stem cells is regulated by cell-substratum adhesion and cell spreading

Patricia Murray*, Marina Prewitz, Isabel Hopp, Nicola Wells, Haifei Zhang, Andrew Cooper, Kristina L. Parry, Robert Short, Daniel J. Antoine, David Edgar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Mouse embryonic stem cells (mESCs) undergo self-renewal in the presence of the cytokine, leukaemia inhibitory factor (LIF). Following LIE withdrawal, mESCs differentiate, and this is accompanied by an increase in cell-substratum adhesion and cell spreading. The purpose of this study was to investigate the relationship between cell spreading and mESC differentiation. Using E14 and R1 mESC lines, we have restricted cell spreading in the absence of LIF by either culturing mESCs on chemically defined, weakly adhesive biomaterial substrates, or by manipulating the cytoskeleton. We demonstrate that by restricting the degree of spreading by either method, mESCs can be maintained in an undifferentiated and pluripotent state. Under these conditions, self-renewal occurs without the need for LIF and is independent of nuclear translocation of tyrosine-phosphorylated STAT3 or beta-catenin, which have previously been implicated in self-renewal. We also demonstrate that the effect of restricted cell spreading on mESC self-renewal is not mediated by increased intercellular adhesion, as evidenced by the observations that inhibition of mESC adhesion using a function blocking anti E-cadherin antibody or siRNA do not promote differentiation. These results show that mESC spreading and differentiation are regulated both by LIE and by cell-substratum adhesion, consistent with the hypothesis that cell spreading is the common intermediate step in the regulation of mESC differentiation by either LIP or cell-substratum adhesion. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)2698-2705
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume45
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Embryonic stem cells
  • Cell spreading
  • Biomaterials
  • E-cadherin
  • Rho kinase
  • E-CADHERIN
  • FATE DECISIONS
  • ROCK INHIBITOR
  • DIFFERENTIATION
  • PLURIPOTENCY
  • GROWTH
  • SHAPE
  • LIF
  • CYTOSKELETON
  • EXPRESSION

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