1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest Bond Avenue, Portland, Oregon 97239, USA [2] Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 Northwest 185th Avenue, Beaverton, Oregon 97006, USA [3].
1] Department of Reproductive Medicine, University of California, San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, California 92037, USA [2].
Nature. 2014 Jul 10;511(7508):177-83. doi: 10.1038/nature13551. Epub 2014 Jul 2.
Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the 'gold standard', they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies.
人类多能干细胞在再生医学方面具有潜力，但现有的细胞类型存在显著的局限性。尽管体外受精胚胎（IVF ES 细胞）来源的胚胎干细胞（ES 细胞）代表了“金标准”，但它们与患者存在异体性。自体诱导多能干细胞（iPS 细胞）易发生表观遗传和转录异常。为了确定这些异常是体细胞重编程的固有特性还是重编程方法的次要因素，对通过体细胞核移植（SCNT）获得的遗传匹配的一组人类 IVF ES 细胞、iPS 细胞和核移植 ES 细胞（NT ES 细胞）进行了全基因组分析。源自同一体细胞的 NT ES 细胞和 iPS 细胞都含有数量相当的从头拷贝数变异。相比之下，NT ES 细胞的 DNA 甲基化和转录组谱与 IVF ES 细胞非常相似，而 iPS 细胞则不同，并保留了典型的亲本体细胞的残留 DNA 甲基化模式。因此，人类体细胞可以通过 SCNT 被忠实地重编程为多能性，因此非常适合细胞替代疗法。
