Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells.
Induced pluripotent stem cell generation-associated point mutations arise during the initial stages of the conversion of these cells.
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DOI：
10.1016/j.stemcr.2013.11.006
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发表时间：
2014-01-14
影响因子：
5.9
通讯作者：
Abe M
中科院分区：
文献类型：
--
作者：
Sugiura M;Kasama Y;Araki R;Hoki Y;Sunayama M;Uda M;Nakamura M;Ando S;Abe M
迄今为止，在诱导多能干细胞（iPSC）基因组中已经发现了大量的点突变。这些突变是否与iPSC的产生有关是一个重要而有争议的问题。在这项研究中，我们以不同的方式解决了这一关键问题，包括对iPSC与胚胎干细胞（ESCs）的评估，以及对单个iPSC克隆中变异等位基因频率和点突变异质性的研究。通过这些分析，我们获得了强有力的证据，证明ipsc生成相关的点突变在细胞谱系转换开始后经常以转化为主的方式发生。iPSC克隆内点突变谱的异质性也被揭示，并反映了每个突变的出现历史。此外，我们的研究结果提出了一种构建具有较少点突变的iPSCs的可能方法。iPSC与escs -点突变频率和模式的明显差异大量iPSC世代相关的点突变，而不是先前存在的点突变在iPSC克隆中点突变谱的异质性iPSC克隆中没有共同的点突变Sugiura等人已经获得了强有力的证据，表明iPSC世代相关的点突变在细胞谱系转换开始后经常以逆转为主的方式发生。iPSC克隆内点突变谱的异质性也被揭示，并反映了每个突变的出现历史。
A large number of point mutations have been identified in induced pluripotent stem cell (iPSC) genomes to date. Whether these mutations are associated with iPSC generation is an important and controversial issue. In this study, we approached this critical issue in different ways, including an assessment of iPSCs versus embryonic stem cells (ESCs), and an investigation of variant allele frequencies and the heterogeneity of point mutations within a single iPSC clone. Through these analyses, we obtained strong evidence that iPSC-generation-associated point mutations occur frequently in a transversion-predominant manner just after the onset of cell lineage conversion. The heterogeneity of the point mutation profiles within an iPSC clone was also revealed and reflects the history of the emergence of each mutation. Further, our results suggest a possible approach for establishing iPSCs with fewer point mutations. iPSCs versus ESCs—an obvious difference in the frequency and mode of point mutations A large number of iPSC generation-associated, not preexisting, point mutations Heterogeneity of point mutation profiles in an iPSC clone No common point mutations among iPSC clones Sugiura et al. have obtained strong evidence that iPSC generation-associated point mutations occur frequently in a transversion-predominant manner just after the onset of cell lineage conversion. The heterogeneity of the point mutation profiles within an iPSC clone was also revealed and reflects the history of the emergence of each mutation.