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

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. Leibel, Douglas A. Melton and Kevin Eggan ()
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Dieter Egli: Harvard University
Alice E. Chen: 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
Kevin Eggan: Harvard University

Nature Communications, 2011, vol. 2, issue 1, 1-10

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1503

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