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Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells

Nature Biotechnology volume 29, pages 11171119 (2011) | Download Citation

  • An Erratum to this article was published on 09 January 2012

This article has been updated

Abstract

We compared bona fide human induced pluripotent stem cells (iPSCs) derived from umbilical cord blood (CB) cells and neonatal keratinocytes (K). As a consequence of both incomplete erasure of tissue-specific methylation and aberrant de novo methylation, CB-iPSCs and K-iPSCs were distinct in genome-wide DNA methylation profiles and differentiation potential. Extended passage of some iPSC clones in culture did not improve their epigenetic resemblance to embryonic stem cells, implying that some human iPSCs retain a residual 'epigenetic memory' of their tissue of origin.

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  • 09 January 2012

    In the version of this article initially published, the received date was incorrect. The correct received date is 17 February 2011. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

G.Q.D. was funded by US National Institutes of Health (NIH) grants DK70055 and DK59279, special funds received by the NIH under the American Recovery and Reinvestment Act (RC2-HL102815). K.K. was supported by NIH (K99HL093212-01), Leukemia and Lymphoma Society (3567-07), and Cooley′s Anemia Foundation. A.P.F. was funded by NIH grants R37CA054358 and P50HG003233.

Author information

Author notes

    • Kitai Kim

    Present address: Department of Cancer Biology and Genetics, Center for Cell Engineering, Sloan-Kettering Institute, New York, New York, USA.

    • Kitai Kim
    • , Rui Zhao
    • , Akiko Doi
    •  & Kitwa Ng

    These authors contributed equally to this work.

Affiliations

  1. Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Manton Center for Orphan Disease Research, Howard Hughes Medical Institute, Children's Hospital Boston and Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

    • Kitai Kim
    • , Rui Zhao
    • , Kitwa Ng
    • , Juli Unternaehrer
    • , Patrick Cahan
    • , Huo Hongguang
    • , Yuin-Han Loh
    • , M William Lensch
    •  & George Q Daley
  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA.

    • Kitai Kim
    • , Rui Zhao
    • , Juli Unternaehrer
    • , Patrick Cahan
    • , Yuin-Han Loh
    • , M William Lensch
    •  & George Q Daley
  3. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.

    • Kitai Kim
    • , Rui Zhao
    • , Kitwa Ng
    • , Juli Unternaehrer
    • , Patrick Cahan
    • , Huo Hongguang
    • , Yuin-Han Loh
    • , M William Lensch
    •  & George Q Daley
  4. Center for Epigenetics and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

    • Akiko Doi
    •  & Andrew P Feinberg
  5. Oncology Department, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.

    • Martin J Aryee
  6. Department of Biomedical Engineering and Center for BioDynamics, Boston University, Boston, Massachusetts, USA.

    • Hu Li
    •  & James J Collins
  7. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.; Howard Hughes Medical Institute.

    • James J Collins
  8. Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA.

    • George Q Daley

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Contributions

K.K., R.Z., K.N. and G.Q.D. conceived the experimental plan. K.K., R.Z., A.D., K.N., J.U., H.H., M.W.L., Y.-H.L. and H.L. performed the experiments. K.K., A.D., P.C. and M.J.A. performed data analysis. A.D., M.J.A. and A.P.F. performed CHARM and guided analysis of methylation. K.K., R.Z., A.D., K.N., J.U., P.C., J.J.C., M.W.L., A.P.F. and G.Q.D. wrote the manuscript.

Competing interests

G.Q.D. is a member of the scientific advisory boards of iPierian, Verastem, Epizyme, Solasia, MPM Capital and Johnson & Johnson.

Corresponding authors

Correspondence to Andrew P Feinberg or George Q Daley.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Tables 1–6, Supplementary Methods and Supplementary Figures 1–15

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DOI

https://doi.org/10.1038/nbt.2052

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