Yang Xiangzhong, Smith Sadie L, Tian X Cindy, Lewin Harris A, Renard Jean-Paul, Wakayama Teruhiko
Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Storrs, Connecticut 06269, USA.
Nat Genet. 2007 Mar;39(3):295-302. doi: 10.1038/ng1973.
Therapeutic cloning, whereby somatic cell nuclear transfer (SCNT) is used to generate patient-specific embryonic stem cells (ESCs) from blastocysts cloned by nuclear transfer (ntESCs), holds great promise for the treatment of many human diseases. ntESCs have been derived in mice and cattle, but thus far there are no credible reports of human ntESCs. Here we review the recent literature on nuclear reprogramming by SCNT, including studies of gene expression, DNA methylation, chromatin remodeling, genomic imprinting and X chromosome inactivation. Reprogramming of genes expressed in the inner cell mass, from which ntESCs are derived, seems to be highly efficient. Defects in the extraembryonic lineage are probably the major cause of the low success rate of reproductive cloning but are not expected to affect the derivation of ntESCs. We remain optimistic that human therapeutic cloning is achievable and that the derivation of patient-specific ntESC lines will have great potential for regenerative medicine.
治疗性克隆，即通过体细胞核移植（SCNT）从经核移植克隆的囊胚中生成患者特异性胚胎干细胞（ESC），在治疗多种人类疾病方面具有巨大潜力。小鼠和牛已成功获得了核移植胚胎干细胞（ntESC），但迄今为止，尚无关于人类ntESC的可靠报道。在此，我们综述了近期有关SCNT核重编程的文献，包括基因表达、DNA甲基化、染色质重塑、基因组印记和X染色体失活的研究。从其中获取ntESC的内细胞团中表达的基因重编程似乎效率很高。胚胎外谱系的缺陷可能是生殖克隆成功率低的主要原因，但预计不会影响ntESC的获得。我们仍然乐观地认为，人类治疗性克隆是可以实现的，并且患者特异性ntESC系的获得将在再生医学中具有巨大潜力。
