Egli Dieter, Sandler Vladislav M, Shinohara Mari L, Cantor Harvey, Eggan Kevin
Stowers Medical Institute, Harvard Stem Cell Institute, Department of Stem Cell and Regenerative Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02140, USA.
Curr Biol. 2009 Aug 25;19(16):1403-9. doi: 10.1016/j.cub.2009.06.065. Epub 2009 Aug 13.
It is well known that oocytes can reprogram differentiated cells, allowing animal cloning by nuclear transfer. We have recently shown that fertilized zygotes retain reprogramming activities, suggesting that such activities might also persist in cleavage-stage embryos. Here, we used chromosome transplantation techniques to investigate whether the blastomeres of two-cell-stage mouse embryos can reprogram more differentiated cells. When chromosomes from one of the two blastomeres were replaced with the chromosomes of an embryonic or CD4(+) T lymphocyte donor cell, we observed nuclear reprogramming and efficient contribution of the manipulated cell to the developing blastocyst. Embryos produced by this method could be used to derive stem cell lines and also developed to term, generating mosaic "cloned" animals. These results demonstrate that blastomeres retain reprogramming activities and support the notion that discarded human preimplantation embryos may be useful recipients for the production of genetically tailored human embryonic stem cell lines.
众所周知,卵母细胞能够重编程分化细胞,从而实现通过核移植进行动物克隆。我们最近发现,受精后的合子保留了重编程活性,这表明此类活性可能在卵裂期胚胎中也持续存在。在此,我们运用染色体移植技术来研究二细胞期小鼠胚胎的卵裂球是否能够重编程更分化的细胞。当将两个卵裂球之一的染色体替换为胚胎或CD4(+) T淋巴细胞供体细胞的染色体时,我们观察到了核重编程以及被操控细胞对发育中的囊胚的有效贡献。通过这种方法产生的胚胎可用于建立干细胞系,并且还能发育至足月,产生嵌合的“克隆”动物。这些结果表明卵裂球保留着重编程活性,并支持这样一种观点,即废弃的人类植入前胚胎可能是用于生产基因定制的人类胚胎干细胞系的有用受体。