The Howard Hughes Medical Institute, Stowers Medical Institute, Harvard Stem Cell Institute and Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Development. 2010 Jun;137(12):1953-63. doi: 10.1242/dev.046151. Epub 2010 May 12.
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.
核转移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及其分化程度均被认为是重编程成功的重要决定因素。在这里，我们使用处于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足够的必需核因子（如 Brg1），许多细胞周期阶段都与重编程兼容。与这一结论一致的是，使用来自胚胎细胞的供体核时，重编程效率的提高至少部分可以通过与供体核一起重新引入胚胎核因子来解释。相比之下，只要在第一次有丝分裂时达到同步，供体核与受体细胞之间的细胞周期同步性在转移时并不需要。我们的发现表明了重编程过程的惊人灵活性，并支持核转录调节剂在介导重编程中的重要性。
