title: Reprogramming within hours following nuclear transfer into mouse but not human zygotes.
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.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.forename: Alice E
authors.initials: AE
authors.lastname: Chen
authors.forename: Genevieve
authors.initials: G
authors.lastname: Saphier
authors.forename: Justin
authors.initials: J
authors.lastname: Ichida
authors.forename: Claire
authors.initials: C
authors.lastname: Fitzgerald
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Go
authors.forename: Nicole
authors.initials: N
authors.lastname: Acevedo
authors.forename: Jay
authors.initials: J
authors.lastname: Patel
authors.forename: Manfred
authors.initials: M
authors.lastname: Baetscher
authors.forename: William G
authors.initials: WG
authors.lastname: Kearns
authors.forename: Robin
authors.initials: R
authors.lastname: Goland
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Melton
authors.forename: Kevin
authors.initials: K
authors.lastname: Eggan
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008938:Mitosis; D053652:Nuclear Transfer Techniques; D015053:Zygote / Q000166:cytology*