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.
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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 18 JAN 2012
DOI: 10.1002/stem.793
Copyright © 2011 AlphaMed Press
Additional Information
How to Cite
Sun, B., Ito, M., Mendjan, S., Ito, Y., Brons, I. G. M., Murrell, A., Vallier, L., Ferguson-Smith, A. C. and Pedersen, R. A. (2012), Status of Genomic Imprinting in Epigenetically Distinct Pluripotent Stem Cells. STEM CELLS, 30: 161–168. doi: 10.1002/stem.793
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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.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLSEXPRESS November 22, 2011.
Publication History
- Issue published online: 18 JAN 2012
- Article first published online: 18 JAN 2012
- Accepted manuscript online: 22 NOV 2011 10:11AM EST
- Manuscript Accepted: 5 NOV 2011
- Manuscript Received: 13 JAN 2011
Funded by
- MRC studentship
- U.S. National Institutes of Health/National Institute of Child Health and Human Development
- EU FP7 Grant HEALTH-F4-2009-223485/PluriSys
- MRC program grants
- A.F.S.
- Wellcome Trust grant
- MRC Senior Research Fellowship
- CRUK Senior Cancer Research Fellowship
- AICR grant
- Cambridge University Hospitals National Institute for Health Research Biomedical Research Centre and Evelyn Trust
- Shanghai Jiao Tong University School of Medicine, Shanghai, China
Keywords:
- Mouse embryonic stem cells;
- Mouse epiblast stem cells;
- Mouse induced pluripotent stem cells;
- Epigenetics;
- Imprinting
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.