细胞重编程前后基因组的动态稳定性

背景：研究表明，人类早代诱导多能性干细胞发生拷贝数变异多于晚代、体细胞及人类胚胎干细胞。目的：分析重编程过程是否危及基因组稳定性，进一步探讨诱导多能性干细胞建系的有效性。 方法：利用高分辨率的Affymetrix Cytoscan HD芯片检测遗传性癫痫先证者的体细胞及早代诱导多能性干细胞，分析重编程后基因组拷贝数变异及杂合性缺失的变化。 结果与结论：与遗传性癫痫患者体细胞相比，其早代诱导多能性干细胞的杂合性缺失未发现明显差异，而存在更多的拷贝数变异，且均为微重复，涉及致癌基因。结果证明重编程过程中基因组稳定性动态变化，需要动态监测诱导多能性干细胞保证其基因组稳定性及临床安全性。

Reprogramme-induced genomic stability

BACKGROUND：Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE：To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS：Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION：Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.