Recipient cell nuclear factors are required for reprogramming by nuclear transfer

Recipient cell nuclear factors are required for reprogramming by nuclear transfer
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DOI:
10.1242/dev.046151
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发表时间:
2010-06-15
期刊:
影响因子:
4.6
通讯作者:
Eggan, Kevin
Eggan, Kevin
中科院分区:
生物学2区
文献类型:
--
作者:
Egli, Dieter;Eggan, Kevin

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核移植允许体细胞重编程为全能性。供体和受体细胞的细胞周期状态,以及它们的分化程度,都被认为是重编程成功的重要决定因素。在这里,我们使用不同细胞周期和发育阶段的供体和受体细胞来研究这些参数的重要性。我们发现,只要在去核后受体细胞中保留了足够的基本核因子,如Brg1,细胞周期的许多阶段都与重编程兼容。与这一结论一致,当使用来自胚胎细胞的供体细胞核时,重编程效率的提高可以解释为,至少部分地,与供体细胞核一起重新引入胚胎核因子。相比之下,在移植时,只要第一次有丝分裂达到同步,就不需要供体细胞核和受体细胞之间的细胞周期同步。我们的研究结果证明了重编程过程的显著灵活性,并支持核转录调控因子在介导重编程中的重要性。
Nuclear transfer allows the reprogramming of somatic cells to totipotency. The cell cycle state of the donor and recipient cells, as well as their extent of differentiation, have each been cited as important determinants of reprogramming success. Here, we have used donor and recipient cells at various cell cycle and developmental stages to investigate the importance of these parameters. We found that many stages of the cell cycle were compatible with reprogramming as long as a sufficient supply of essential nuclear factors, such as Brg1, were retained in the recipient cell following enucleation. Consistent with this conclusion, the increased efficiency of reprogramming when using donor nuclei from embryonic cells could be explained, at least in part, by reintroduction of embryonic nuclear factors along with the donor nucleus. By contrast, cell cycle synchrony between the donor nucleus and the recipient cell was not required at the time of transfer, as long as synchrony was reached by the first mitosis. Our findings demonstrate the remarkable flexibility of the reprogramming process and support the importance of nuclear transcriptional regulators in mediating reprogramming.