The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
Stem Cell Unit, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel.
Cell Stem Cell. 2014 Nov 6;15(5):634-42. doi: 10.1016/j.stem.2014.10.002.
The recent finding that reprogrammed human pluripotent stem cells can be derived by nuclear transfer into human oocytes as well as by induced expression of defined factors has revitalized the debate on whether one approach might be advantageous over the other. Here we compare the genetic and epigenetic integrity of human nuclear-transfer embryonic stem cell (NT-ESC) lines and isogenic induced pluripotent stem cell (iPSC) lines, derived from the same somatic cell cultures of fetal, neonatal, and adult origin. The two cell types showed similar genome-wide gene expression and DNA methylation profiles. Importantly, NT-ESCs and iPSCs had comparable numbers of de novo coding mutations, but significantly more than parthenogenetic ESCs. As iPSCs, NT-ESCs displayed clone- and gene-specific aberrations in DNA methylation and allele-specific expression of imprinted genes. The occurrence of these genetic and epigenetic defects in both NT-ESCs and iPSCs suggests that they are inherent to reprogramming, regardless of derivation approach.
最近的研究发现，通过核移植将重编程的人类多能干细胞导入人类卵母细胞，以及通过诱导表达特定因子，都可以获得人类多能干细胞。这一发现再次引发了关于这两种方法哪种更有优势的争论。在这里，我们比较了来源于同一胎儿、新生儿和成人来源的成体细胞培养物的核转移胚胎干细胞（NT-ESC）系和同源诱导多能干细胞（iPSC）系的遗传和表观遗传完整性。两种细胞类型表现出相似的全基因组基因表达和 DNA 甲基化谱。重要的是，NT-ESCs 和 iPSCs 具有相似数量的新生编码突变，但明显多于孤雌胚胎干细胞。作为 iPSCs，NT-ESCs 在 DNA 甲基化和印迹基因的等位基因特异性表达中表现出克隆和基因特异性的异常。这些遗传和表观遗传缺陷在 NT-ESCs 和 iPSCs 中均有发生，这表明它们是重编程所固有的，与衍生方法无关。
