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Reprogramming within hours following nuclear transfer into mouse but not human zygotes

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  • Dieter Egli

    (Harvard University
    Harvard Stem Cell Institute, Harvard University
    The New York Stem Cell Foundation Laboratory
    Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University)

  • Alice E. Chen

    (Harvard University
    Harvard Stem Cell Institute, Harvard University)

  • Genevieve Saphier

    (Harvard University)

  • Justin Ichida

    (Harvard University)

  • Claire Fitzgerald

    (Harvard University)

  • Kathryn J. Go

    (Reproductive Science Center)

  • Nicole Acevedo

    (Reproductive Science Center)

  • Jay Patel

    (Reproductive Science Center)

  • Manfred Baetscher

    (Harvard University)

  • William G. Kearns

    (The Center for Preimplantation Genetics)

  • Robin Goland

    (Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University)

  • Rudolph L. Leibel

    (Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University)

  • Douglas A. Melton

    (Harvard University
    Harvard Stem Cell Institute, Harvard University
    Howard Hughes Medical Institute, Harvard University)

  • Kevin Eggan

    (Harvard University
    Harvard Stem Cell Institute, Harvard University
    Howard Hughes Medical Institute, Harvard University)

Abstract

Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation.

Suggested Citation

  • Dieter Egli & Alice E. Chen & Genevieve Saphier & Justin Ichida & Claire Fitzgerald & Kathryn J. Go & Nicole Acevedo & Jay Patel & Manfred Baetscher & William G. Kearns & Robin Goland & Rudolph L. Lei, 2011. "Reprogramming within hours following nuclear transfer into mouse but not human zygotes," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1503
    DOI: 10.1038/ncomms1503
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