Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nat Commun. 2011 Oct 4;2:488. 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.
受精卵可以将体细胞重编程为多能状态。因此，人类受精卵可能有助于产生患者来源的多能干细胞。然而，由于后勤、法律和社会方面的考虑，用于研究的人类卵子的供应受到限制。在这里，我们表明可以获得大量正常受精卵（胚胎）用于重编程研究。使用这些受精卵，我们发现当胚胎基因组被体细胞基因组取代时，胚胎在卵裂阶段的发育正常进行，但随后在桑葚胚阶段之前停止。这种停滞与转移的体细胞基因组中转录激活的失败有关。与人类受精卵不同，小鼠受精卵在转移后数小时内将体细胞基因组重编程为多能状态。我们的结果表明，人类核转移可能存在以前未被认识到的障碍，未来的研究可以集中在基因组激活的要求上。
