High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity
High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity
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DOI：
10.1038/nbt.1615
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发表时间：
2010-04-01
影响因子：
46.9
通讯作者：
Lahesmaa, Riitta
中科院分区：
文献类型：
--
作者：
Narva, Elisa;Autio, Reija;Lahesmaa, Riitta
人类胚胎干细胞（hESC）的长期培养可能导致适应和染色体异常的获得，强调了对这些细胞进行严格遗传分析的必要性。在这里，我们报告了迄今为止最高分辨率的hESC研究，使用包含906，600个单核苷酸多态性（SNP）探针和946，000个拷贝数变异（CNV）探针的Affyphase SNP 6.0阵列。对不同实验室中保存的17个不同hESC系的分析鉴定出843个大小为50 kb-3 Mb的CNV。我们发现，在同一品系的早期和晚期传代之间，平均有24%的杂合性缺失（洛合性）位点和66%的CNV在培养中发生了变化。与正常拷贝数状态的样本相比，在CNV位点内检测到的基因中有30%的表达发生了改变，其中>44%的基因在功能上与癌症相关。此外，在hESC中检测到了16号染色体q臂的洛缺失，这在以前的研究中还没有观察到。
Prolonged culture of human embryonic stem cells (hESCs) can lead to adaptation and the acquisition of chromosomal abnormalities, underscoring the need for rigorous genetic analysis of these cells. Here we report the highest-resolution study of hESCs to date using an Affymetrix SNP 6.0 array containing 906,600 probes for single nucleotide polymorphisms (SNPs) and 946,000 probes for copy number variations (CNVs). Analysis of 17 different hESC lines maintained in different laboratories identified 843 CNVs of 50 kb-3 Mb in size. We identified, on average, 24% of the loss of heterozygosity (LOH) sites and 66% of the CNVs changed in culture between early and late passages of the same lines. Thirty percent of the genes detected within CNV sites had altered expression compared to samples with normal copy number states, of which >44% were functionally linked to cancer. Furthermore, LOH of the q arm of chromosome 16, which has not been observed previously in hESCs, was detected.