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

• Published in: Nature communications Vol. 2; no. 1; p. 488
• Main Authors: Egli, Dieter, Chen, Alice E., Saphier, Genevieve, Ichida, Justin, Fitzgerald, Claire, Go, Kathryn J., Acevedo, Nicole, Patel, Jay, Baetscher, Manfred, Kearns, William G., Goland, Robin, Leibel, Rudolph L., Melton, Douglas A., Eggan, Kevin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2011; Nature Publishing Group
• Subjects: 631/136/2435; 631/136/532/2064/2117; 631/1647/1513; 692/698/690/1520; Animals; Arrests; DNA methylation; Donations; Genomes; Humanities and Social Sciences; Humans; Medical research; Mice; Mitosis; multidisciplinary; Nuclear Transfer Techniques; Science; Science (multidisciplinary); Stem cells; Zygote - cytology; New York; United States > US; Massachusetts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1503

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. The generation of human cell lines using somatic cell nuclear transfer has been difficult to achieve. In this study, Egli et al . show that while mouse eggs reprogram somatic cells within hours, human eggs arrest after nuclear transfer which may be due to a lack of genome transcription.