Canonical Wnt Signaling Induces a Primitive Endoderm Metastable State in Mouse Embryonic Stem Cells§

Authors

  • Feodor D. Price,

    1. Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada
    2. Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    Search for more papers by this author
  • Hang Yin,

    1. Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada
    2. Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    Search for more papers by this author
  • Andrew Jones,

    1. Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada
    2. Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    Search for more papers by this author
  • Wilfred van Ijcken,

    1. ERASMUS Center for Biomics, Rotterdam, The Netherlands
    Search for more papers by this author
  • Frank Grosveld,

    1. ERASMUS Center for Biomics, Rotterdam, The Netherlands
    Search for more papers by this author
  • Michael A. Rudnicki

    Corresponding author
    1. Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, Ottawa, Ontario, Canada
    2. Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
    • Sprott Center For Stem Cell Research, Ottawa Hospital Research Institute, Regenerative Medicine Program, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6
    Search for more papers by this author
    • Telephone: 613-739-6740; Fax: 613-739-6294


  • Author contributions: F.P.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and financial support; H.Y.: collection and/or assembly of data and data analysis and interpretation; A.J.: collection and/or assembly of data; W.I.: collection and/or assembly of data; F.G.: financial support; M.R.: conception and design, data analysis and interpretation, manuscript writing, and financial support.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS January 10, 2013.

Abstract

Activation of the canonical Wnt signaling pathway synergizes with leukemia inhibitory factor (LIF) to maintain pluripotency of mouse embryonic stem cells (mESCs). However, in the absence of LIF, Wnt signaling is unable to maintain ESCs in the undifferentiated state. To investigate the role of canonical Wnt signaling in pluripotency and lineage specification, we expressed Wnt3a in mESCs and characterized them in growth and differentiation. We found that activated canonical Wnt signaling induced the formation of a reversible metastable primitive endoderm state in mESC. Upon subsequent differentiation, Wnt3a-stimulated mESCs gave rise to large quantities of visceral endoderm. Furthermore, we determined that the ability of canonical Wnt signaling to induce a metastable primitive endoderm state was mediated by Tbx3. Our data demonstrates a specific role for canonical Wnt signaling in promoting pluripotency while at the same time priming cells for subsequent differentiation into the primitive endoderm lineage. STEM CELLS 2013;31:752–764

Ancillary