Genome-wide CNV analysis in mouse induced pluripotent stem cells reveals dosage effect of pluripotent factors on genome integrity.
Genome-wide CNV analysis in mouse induced pluripotent stem cells reveals dosage effect of pluripotent factors on genome integrity.
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小鼠诱导多能干细胞的全基因组 CNV 分析揭示多能因子对基因组完整性的剂量效应
DOI：
10.1186/1471-2164-15-79
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发表时间：
2014-01-28
期刊：
影响因子：
4.4
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Chen Y;Guo L;Chen J;Zhao X;Zhou W;Zhang C;Wang J;Jin L;Pei D;Zhang F
背景体细胞来源的诱导多能干细胞（Induced pluripotent stem cells，iPSCs）具有巨大的临床应用潜力。值得注意的是，最近报道，从体细胞到iPSC的重编程可以诱导基因组拷贝数变异（CNV），这是人类疾病的主要遗传原因之一。然而，目前尚不清楚这种基因组不稳定性是否取决于重编程方法和/或供体细胞的遗传背景。此外，全基因组的CNV分析是技术上的挑战和CNV数据需要解释carry. ResultsTo仔细研究可能的CNV不稳定性在体细胞重编程，我们进行了全基因组的CNV分析与41小鼠iPSC线从同一个亲本供体，因此，供体的遗传背景可以控制。不同的重编程因子组合和剂量用于研究对基因组完整性的潜在方法依赖性影响。我们使用高分辨率比较基因组杂交检测到63个iPSC CNVs。有趣的是，CNV率与经典因子的剂量呈负相关。此外，使用高性能的工程因子导致更少的CNVs比经典的因素（S）相同的dosage.ConclusionOur的观察表明，足够的重编程力可以保护基因组从CNV不稳定的重编程过程中。
BackgroundInduced pluripotent stem cells (iPSCs) derived from somatic cells have enormous potential for clinical applications. Notably, it was recently reported that reprogramming from somatic cells to iPSCs can induce genomic copy number variation (CNV), which is one of the major genetic causes of human diseases. However it was unclear if this genome instability is dependent on reprogramming methods and/or the genetic background of donor cells. Furthermore, genome-wide CNV analysis is technically challenging and CNV data need to be interpreted with care.ResultsIn order to carefully investigate the possible CNV instability during somatic reprogramming, we performed genome-wide CNV analyses with 41 mouse iPSC lines generated from the same parental donor; therefore, the donor’s genetic background can be controlled. Different reprogramming factor combinations and dosages were used for investigating potential method-dependent effects on genome integrity. We detected 63 iPSC CNVs using high-resolution comparative genomic hybridization. Intriguingly, CNV rates were negatively associated with the dosages of classic factor(s). Furthermore, the use of high-performance engineered factors led to less CNVs than the classic factor(s) of the same dosage.ConclusionOur observations suggest that sufficient reprogramming force can protect the genome from CNV instability during the reprogramming process.
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影响因子：
46.9
作者：
通讯作者：
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影响因子：
64.5
作者：
Hanna JH;Saha K;Jaenisch R
通讯作者：
Jaenisch R
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
64.8
作者：
Robinton, Daisy A.;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya