Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs.
Mouse SCNT ESCs have lower somatic mutation load than syngeneic iPSCs.
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DOI：
10.1016/j.stemcr.2014.02.005
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发表时间：
2014-04-08
影响因子：
5.9
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Li, Zhe;Lu, Hongxia;Yang, Weifeng;Yong, Jun;Zhang, Zhen-ning;Zhang, Kun;Deng, Hongkui;Xu, Yang
重编程因子的异位表达已被广泛应用于体细胞核重编程，使其进入多能状态（诱导多能干细胞[iPSCs]）。然而，遗传畸变，如体细胞基因突变在由此产生的iPSCs引起了对其临床应用的关注。为了测试增加的体细胞突变是否主要是当前重编程方法的副产品，我们将近交C57BL/6小鼠的胚胎成纤维细胞重编程为iPSCs（8个系，先前发表的4个系）或体细胞核移植胚胎干细胞（SCNT ESCs， 11个系）。这些细胞系的外显子组测序表明，SCNT ESCs的突变负荷明显低于具有同基因背景的iPSCs。此外，一个SCNT-ESC系没有检测到外显子组突变，两对SCNT-ESC系只有共同的预先存在的突变。相比之下，每个iPSC系都携带独特的突变。我们的研究强调了在更多生理相关条件下改进重编程方法的必要性。体细胞核转移-胚胎干细胞（SCNT- esc）或异位表达重编程因子（诱导多能干细胞[iPSC]）对近交C57BL/6小鼠胚胎成纤维细胞重编程的多能干细胞系进行外显子组测序，获得体细胞核转移-胚胎干细胞（SCNT- esc）或重编程因子（诱导多能干细胞[iPSC]）他们的研究表明，SCNT-ESC系的体细胞编码突变负荷明显低于iPSC系。
Ectopic expression of reprogramming factors has been widely adopted to reprogram somatic nucleus into a pluripotent state (induced pluripotent stem cells [iPSCs]). However, genetic aberrations such as somatic gene mutation in the resulting iPSCs have raised concerns regarding their clinical utility. To test whether the increased somatic mutations are primarily the by-products of current reprogramming methods, we reprogrammed embryonic fibroblasts of inbred C57BL/6 mice into either iPSCs (8 lines, 4 previously published) or embryonic stem cells (ESCs) with somatic cell nuclear transfer (SCNT ESCs; 11 lines). Exome sequencing of these lines indicates a significantly lower mutation load in SCNT ESCs than iPSCs of syngeneic background. In addition, one SCNT-ESC line has no detectable exome mutation, and two pairs of SCNT-ESC lines only have shared preexisting mutations. In contrast, every iPSC line carries unique mutations. Our study highlights the need for improving reprogramming methods in more physiologically relevant conditions. Comparison of somatic-coding mutation load in SCNT ESCs and iPSCs in mice Lower mutational load in SCNT ESCs than iPSCs of syngeneic background By exome sequencing of pluripotent stem cell lines reprogrammed from embryonic fibroblasts of inbred C57BL/6 mice with somatic cell nuclear transfer-embryonic stem cell (SCNT-ESC) or ectopic expression of reprogramming factors (induced pluripotent stem cells [iPSC]), Zhang, Deng, Xu, and colleagues show that the SCNT-ESC lines harbor a significantly lower somatic-coding mutation load than iPSC lines.
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影响因子：
64.8
作者：
Wakayama, T;Perry, ACF;Yanagimachi, R
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1202352109
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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作者：
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作者：
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