Kevin Eggan2014-02-27 12:40 PM

Reprogramming within hours following nuclear transfer into mouse but not human zygotes. 重编程数小时内随核移植进入小鼠而非人类的受精卵 

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.

论文摘要

已受精的小鼠受精卵可将体细胞重编程为多能状态。因此人类受精卵可有效用于源自患者的多能干细胞的生产。 然而逻辑,法律和社会方面的顾虑限制了用作研究的人类卵子的获得。我们在此表明可获得大量正常受精卵(合子)来用作重编程研究。使用这些受精卵,我们发现当合子基因被替换为体细胞基因时,发育在整个卵裂阶段仍正常进行,但会在桑椹期前停止。这一抑止与转基因体细胞中的转录激活故障有关。与人类受精卵相反,小鼠受精卵在移植后数小时即将体细胞基因组重编程为多能状态。我们的结果表明这可能是先前阻碍人类核移植成功的未被重视的原因,未来进行的研究可重点聚焦于基因组激活。

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Kevin Eggan

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