Reprogramming within hours following nuclear transfer into mouse but not human zygotes
Reprogramming within hours following nuclear transfer into mouse but not human zygotes
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DOI：
10.1038/ncomms1503
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发表时间：
2011-10-01
影响因子：
16.6
通讯作者：
Eggan, Kevin
中科院分区：
文献类型：
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作者：
Egli, Dieter;Chen, Alice E.;Eggan, Kevin
受精的小鼠受精卵可以将体细胞重新编程为多能状态。因此，人类受精卵可能有助于生产患者来源的多能干细胞。然而，后勤、法律和社会方面的考虑限制了人类卵子用于研究的可能性。在这里，我们表明，可以获得相当数量的正常受精卵(受精卵)用于重新编程研究。利用这些受精卵，我们发现，当合子基因组被体细胞的基因组取代时，整个卵裂阶段的发育正常进行，但在桑拿期之前就停止了。这种停滞与未能激活转移的体细胞基因组中的转录有关。与人类受精卵不同，小鼠受精卵在移植后数小时内将体细胞基因组重新编程为多能状态。我们的结果表明，成功的人类核移植可能存在以前没有意识到的障碍，未来的研究可能会集中在基因组激活的要求上。
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.