Centre for Stem Cell Biology, Department of Biomedical Science, The University of Sheffield, Sheffield, UK.
Nat Biotechnol. 2011 Nov 27;29(12):1132-44. doi: 10.1038/nbt.2051.
The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.
国际干细胞倡议分析了 125 个人胚胎干细胞 (ES) 系和 11 个人诱导多能干细胞 (iPS) 系,这些细胞系来自全球 38 个实验室,研究培养过程中发生的遗传变化。大多数系在早期和晚期传代时进行了分析。单核苷酸多态性 (SNP) 分析表明,它们包括大多数主要种族群体的代表。大多数系仍保持染色体核型正常,但随着培养时间的延长,存在获得变化的趋势,常见于染色体 1、12、17 和 20。DNA 甲基化模式随机变化,与培养时间无关。从 SNP 阵列确定的结构变异也偶尔出现。在染色体 1、12 和 17 上没有观察到与培养相关的常见变异,但在染色体 20q11.21 上出现了一个最小的扩增子,包括三个在人类 ES 细胞中表达的基因 ID1、BCL2L1 和 HM13,该扩增子出现在超过 20%的系中。在这些基因中,BCL2L1 是驱动 ES 细胞培养适应的强有力候选基因。