Status of Genomic Imprinting in Epigenetically Distinct Pluripotent Stem Cells§

Authors

  • Bowen Sun,

    1. The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom
    Search for more papers by this author
  • Mitsuteru Ito,

    1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Search for more papers by this author
  • Sasha Mendjan,

    1. The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom
    Search for more papers by this author
  • Yoko Ito,

    1. Department of Oncology, University of Cambridge, Cambridge, United Kingdom
    2. Cambridge Research Institute, Cancer Research UK, Li Ka Shing Centre, Cambridge, United Kingdom
    Search for more papers by this author
  • I. Gabrielle M. Brons,

    1. The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom
    Search for more papers by this author
  • Adele Murrell,

    1. Department of Oncology, University of Cambridge, Cambridge, United Kingdom
    2. Cambridge Research Institute, Cancer Research UK, Li Ka Shing Centre, Cambridge, United Kingdom
    Search for more papers by this author
  • Ludovic Vallier,

    1. The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom
    Search for more papers by this author
  • Anne C. Ferguson-Smith,

    Corresponding author
    1. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    • Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom
    Search for more papers by this author
    • Telephone: 44(0)1223-333834; Fax: 44(0)1223-333840

  • Roger A. Pedersen

    Corresponding author
    1. The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom
    • The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge CB2 0SZ, United Kingdom
    Search for more papers by this author
    • Author contributions: B.S.: collection and assembly of data, data analysis and interpretation, and manuscript writing; M.I.: data collection, analysis and interpretation; S.M. and Y.I.: data analysis and interpretation; I.G.B.: data collection; A.M.: conception and design and provision of study material; L.V.: provision of study material; A.C.F.-S.: conception and design, financial support, and final approval of manuscript; R.A.P.: conception and design, financial support, manuscript writing, and final approval of manuscript.

    • Telephone: 44-(0)1223-763236; Fax: 44-(0)1223-763350


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

  • §

    First published online in STEM CELLSEXPRESS November 22, 2011.

Abstract

Mouse epiblast stem cells (EpiSCs) derived from postimplantation embryos are developmentally and functionally different from embryonic stem cells (ESCs) generated from blastocysts. EpiSCs require Activin A and FGF2 signaling for self-renewal, similar to human ESCs (hESCs), while mouse ESCs require LIF and BMP4. Unlike ESCs, EpiSCs have undergone X-inactivation, similar to the tendency of hESCs. The shared self-renewal and X-inactivation properties of EpiSCs and hESCs suggest that they have an epigenetic state distinct from ESCs. This hypothesis predicts that EpiSCs would have monoallelic expression of most imprinted genes, like that observed in hESCs. Here, we confirm this prediction. By contrast, we find that mouse induced pluripotent stem cells (iPSCs) tend to lose imprinting similar to mouse ESCs. These findings reveal that iPSCs have an epigenetic status associated with their pluripotent state rather than their developmental origin. Our results also reinforce the view that hESCs and EpiSCs are in vitro counterparts, sharing an epigenetic status distinct from ESCs and iPSCs. STEM CELLS 2012; 30:161–168.

Ancillary