Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
Nat Biotechnol. 2010 Apr;28(4):371-7. doi: 10.1038/nbt.1615. Epub 2010 Mar 28.
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.
长期培养人类胚胎干细胞（hESC）可能导致适应和获得染色体异常，这突显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使用 Affymetrix SNP 6.0 阵列对 hESC 进行的最高分辨率研究，该阵列包含 906,600 个用于单核苷酸多态性（SNP）的探针和 946,000 个用于拷贝数变异（CNV）的探针。对在不同实验室中维持的 17 种不同 hESC 系进行分析，确定了大小为 50 kb-3 Mb 的 843 个 CNV。我们发现，在同一系的早期和晚期传代之间的培养过程中，平均有 24%的杂合性丢失（LOH）位点和 66%的 CNV 发生变化。与具有正常拷贝数状态的样本相比，在 CNV 位点检测到的 30%的基因表达发生改变，其中>44%与癌症功能相关。此外，还检测到先前在 hESC 中未观察到的 16 号染色体 q 臂的 LOH。
