Identification and Classification of Chromosomal Aberrations in Human Induced Pluripotent Stem Cells
Identification and Classification of Chromosomal Aberrations in Human Induced Pluripotent Stem Cells
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DOI：
10.1016/j.stem.2010.07.017
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发表时间：
2010-10-08
期刊：
影响因子：
23.9
通讯作者：
Benvenisty, Nissim
中科院分区：
文献类型：
--
作者：
Mayshar, Yoav;Ben-David, Uri;Benvenisty, Nissim
由于其起源于体细胞，人类诱导多能干细胞(HiPSCs)被认为携带正常的二倍体基因组，适应性染色体异常还没有得到充分的评估。在这里，我们用全局基因表达荟萃分析方法分析了来自18个不同研究的66个HiPSC和38个人类胚胎干细胞(HESC)的染色体完整性。我们报告了大量携带全部和部分染色体异常的细胞系的鉴定，其中一半在DNA水平上得到了验证。一些变异是由培养适应引起的，另一些则被怀疑来自亲本体细胞。我们的分类揭示了第三种类型的非整倍体在早期传代的HiPSCs中已经很明显，这表明在重新编程过程中有相当大的选择压力。分析表明，12号染色体的重复频率很高，导致与细胞周期相关的基因显著丰富。这种非整倍体可能限制了hPSCs的分化能力，增加了hPSCs的致瘤性。
Because of their somatic cell origin, human induced pluripotent stem cells (HiPSCs) are assumed to carry a normal diploid genome, and adaptive chromosomal aberrations have not been fully evaluated. Here, we analyzed the chromosomal integrity of 66 HiPSC and 38 human embryonic si:em cell (HESC) samples from 18 different studies by global gene expression meta-analysis. We report identification of a substantial number of cell lines carrying full and partial chromosomal aberrations, half of which were validated at the DNA level. Several aberrations resulted from culture adaptation, and others are suspected to originate from the parent somatic cell. Our classification revealed a third type of aneuploidy already evident in early passage HiPSCs, suggesting considerable selective pressure during the reprogramming process. The analysis indicated high incidence of chromosome 12 duplications, resulting in significant enrichment for cell cycle-related genes. Such aneuploidy may limit the differentiation capacity and increase the tumorigenicity of HiPSCs.