Comparable Frequencies of Coding Mutations and Loss of Imprinting in Human Pluripotent Cells Derived by Nuclear Transfer and Defined Factors
Comparable Frequencies of Coding Mutations and Loss of Imprinting in Human Pluripotent Cells Derived by Nuclear Transfer and Defined Factors
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DOI：
10.1016/j.stem.2014.10.002
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发表时间：
2014-11-06
期刊：
影响因子：
23.9
通讯作者：
Egli, Dieter
中科院分区：
文献类型：
--
作者：
Johannesson, Bjarki;Sagi, Ido;Egli, Dieter
最近的发现，重编程的人类多能干细胞可以通过核转移到人类卵母细胞以及通过诱导表达的定义的因素，重新激活了辩论是否一种方法可能是优于其他。在这里，我们比较了人核移植胚胎干细胞（NT-ESC）系和同基因诱导多能干细胞（iPSC）系的遗传和表观遗传完整性，这些细胞系来自胎儿、新生儿和成人来源的相同体细胞培养物。两种细胞类型显示出相似的全基因组基因表达和DNA甲基化谱。重要的是，NT-ESC和iPSC具有相当数量的从头编码突变，但显著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方面显示出克隆特异性和基因特异性畸变。NT-ESC和iPSC中这些遗传和表观遗传缺陷的发生表明，无论衍生方法如何，它们都是重编程所固有的。
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.