Stem Cell Institute, University of Connecticut, Farmington, Connecticut, USA.
Stem Cells. 2012 Jan;30(1):22-7. doi: 10.1002/stem.705.
The usefulness of human induced pluripotent stem cells (hiPSCs) in research and therapeutic applications highly relies on their genomic integrity and stability. Many laboratories including ours have addressed this concern by comparing genomic (at both karyotypic and subkaryotypic levels) and epigenomic abnormalities of hiPSC lines (derived via either DNA- or non-DNA-based methods), as well as human embryonic stem cell lines during long-term culture. A variety of methods have been used for this purpose, such as karyotyping and fluorescent in situ hybridization to detect karyotypic abnormalities, array-based comparative genomic hybridization to detect copy number variations (CNVs), single-nucleotide polymorphism-based microarrays to detect both CNVs and loss of heterozygosity, analysis of integration sites in the genome, and whole genome sequencing for protein-coding exome and DNA methylome profiling. Here, we summarize the progresses in this dynamically evolving field and also discuss how the findings apply to the study and application of hiPSCs.
人诱导多能干细胞（hiPSC）在研究和治疗应用中的有用性高度依赖于其基因组的完整性和稳定性。包括我们实验室在内的许多实验室通过比较 hiPSC 系（通过 DNA 或非 DNA 方法衍生）以及人类胚胎干细胞系在长期培养过程中的基因组（在核型和亚核型水平上）和表观基因组异常来解决这一问题。为此，已经使用了多种方法，例如核型分析和荧光原位杂交以检测核型异常，基于阵列的比较基因组杂交以检测拷贝数变异（CNV），基于单核苷酸多态性的微阵列以检测 CNV 和杂合性丢失，整合位点分析基因组，以及全基因组测序用于蛋白质编码外显子和 DNA 甲基组谱分析。在这里，我们总结了这一快速发展领域的进展，并讨论了这些发现如何适用于 hiPSC 的研究和应用。
