ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable
ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable
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DOI：
10.1073/pnas.0510485103
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发表时间：
2006-01-24
影响因子：
11.1
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Brambrink, T;Hochedlinger, K;Jaenisch, R
生殖性克隆作为一种有效的人类技术被一致拒绝，因为在克隆动物中发现了严重异常的表型。在克隆动物的组织中观察到的基因表达畸变也引起了对通过从患者的体细胞进行核移植（NT）而衍生的“定制”胚胎干（ES）细胞的治疗应用的关注。尽管之前的小鼠实验已经证明克隆胚泡来源的ES细胞（NT-ES细胞）的发育潜力与受精胚泡来源的ES细胞的发育潜力相同，但缺乏对NT-ES细胞系的系统性分子表征。为了研究是否转录畸变，类似于克隆小鼠组织中观察到的，也发生在NT-ES细胞，我们比较了10个小鼠NT和受精衍生的ES细胞系的转录谱。我们在这里报告，来自克隆和受精的小鼠囊胚的ES细胞系是不可区分的基础上，他们的转录谱，符合其正常的发育潜力。我们的研究结果表明，在胚胎和胎儿发育的克隆，NT-ES细胞衍生的过程中严格选择那些不朽的细胞，已经删除了“表观遗传记忆”的供体细胞核，因此，成为功能等同。我们的研究结果支持这样的观点，即来自克隆或受精囊胚的ES细胞系具有相同的治疗潜力。
Reproductive cloning is uniformly rejected as a valid technology in humans because of the severely abnormal phenotypes seen in cloned animals. Gene expression aberrations observed in tissues of cloned animals have also raised concerns regarding the therapeutic application of "customized" embryonic stem (ES) cells derived by nuclear transplantation (NT) from a patient's somatic cells. Although previous experiments in mice have demonstrated that the developmental potential of ES cells derived from cloned blastocysts (NT-ES cells) is identical to that of ES cells derived from fertilized blastocysts, a systematic molecular characterization of NT-ES cell lines is lacking. To investigate whether transcriptional aberrations, similar to those observed in tissues of cloned mice, also occur in NT-ES cells, we have compared transcriptional profiles of 10 mouse NT- and fertilization-derived-ES cell lines. We report here that the ES cell lines derived from cloned and fertilized mouse blastocysts are indistinguishable based on their transcriptional profiles, consistent with their normal developmental potential. Our results indicate that, in contrast to embryonic and fetal development of clones, the process of NT-ES cell derivation rigorously selects for those immortal cells that have erased the "epi-genetic memory" of the donor nucleus and, thus, become functionally equivalent. Our findings support the notion that ES cell lines derived from cloned or fertilized blastocysts have an identical therapeutic potential.