Generation of cloned mice by direct nuclear transfer from natural killer T cells
Generation of cloned mice by direct nuclear transfer from natural killer T cells
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DOI：
10.1016/j.cub.2005.05.021
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发表时间：
2005-06-21
期刊：
影响因子：
9.2
通讯作者：
Ogura, A
中科院分区：
文献类型：
--
作者：
Inoue, K;Wakao, H;Ogura, A
通过核移植(NT)克隆哺乳动物的效率仍然很低。一个根本的问题是，克隆是否真的来自分化细胞，而不是来自捐赠者细胞样本中存在的稀有干细胞。到目前为止，具有遗传分化标记的细胞，如成熟淋巴细胞，仅通过涉及胚胎干细胞生成和四倍体互补的两步NT被克隆来产生小鼠[1-3]。在这里，我们展示了一种独特的T细胞群体，自然杀伤T(NKT)细胞的基因组，可以通过一步NT完全重新编程。幼鼠和它们的胎盘具有NKT细胞特有的重排TCR基因座。NKT细胞克隆的胚胎在体外具有很高的发育潜力：大多数(71%)发育到桑椹/囊胚阶段，而来自外周血T细胞的胚胎(12%；p<；1×10(-25))形成了鲜明的对比。此外，从这些NKT细胞囊胚中有效地建立了ES细胞系。这些发现清楚地表明NKT细胞基因组具有很高的可塑性。因此，基因组的分化并不总是克隆NT的障碍，无论是出于生殖还是治疗目的，所以我们现在可以假设，到目前为止，至少有一些克隆的哺乳动物确实是从分化的供体细胞衍生而来的。
Cloning mammals by nuclear transfer (NT) remains inefficient. One fundamental question is whether clones have really been derived from differentiated cells rather than from rare stem cells present in donor-cell samples. To date, cells, such as mature lymphocytes, with genetic differentiation markers have been cloned to generate mice only via a two-step NT involving embryonic stem (ES) cell generation and tetraploid complementation [1-3]. Here, we show that the genome of a unique T-cell population, natural killer T (NKT) cells, can be fully reprogrammed by a single-step NT. The pups and their placentas possessed the rearranged TCR loci specific for NKT cells. The NKT-cell-cloned embryos had a high developmental potential in vitro: Most (71%) developed to the morula/blastocyst stage, in marked contrast to embryos from peripheral blood T cells (12%; p < 1 x 10(-25)). Furthermore, ES cell lines were efficiently established from these NKT-cell blastocysts. These findings clearly indicate a high level of plasticity in the NKT-cell genome. Thus, differentiation of the genome is not always a barrier to NT cloning for either reproductive or therapeutic purposes, so we can now postulate that at least some mammals cloned to date have indeed been derived from differentiated donor cells.