Zheglo Diana, Pozhitnova Victoria O, Kislova Anastasiia V, Markova Zhanna G, Kiselev Danila, Sviridov Philipp S, Sviridova Valeria, Gumerova Lyajsan I, Smirnikhina Svetlana A, Alsalloum Almaqdad, Pylina Svetlana V, Kutsev Sergey Ivanovich, Voronina Ekaterina Sergeevna
Research Centre for Medical Genetics, Moskvorechie 1, Moscow 115478, Russia.
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, Baltiyskaya St. 8, Moscow 125315, Russia.
Int J Mol Sci. 2025 Aug 10;26(16):7728. doi: 10.3390/ijms26167728.
Genome instability in induced pluripotent stem cells (IPSC) poses a significant challenge for their use in research and medicine. Cataloging and precisely describing all the identified aberrations that arise during cell reprogramming, expansion, and differentiation is essential for improving approaches to instability prevention and ensuring genetic quality control. We report the karyotypic analysis of 65 cell lines derived from skin fibroblasts, urinal sediment, and peripheral blood mononuclear cells of 33 individuals, 82% of whom suffer from monogenic genetic disorders not associated with genetic instability. Trisomy of chromosomes 20 and 8 was revealed recurrently, while the 1q arm was the most frequently affected region involved in interstitial duplications and unbalanced translocations with chromosomes 15 and 18. The localization of rearrangement breakpoints identified by SNP arrays within the large gene and histone gene clusters links genetic instability in IPSCs to replication-stress-induced chromosome breakage at common and early replicating fragile sites.
诱导多能干细胞（iPSC）中的基因组不稳定性对其在研究和医学中的应用构成了重大挑战。对细胞重编程、扩增和分化过程中出现的所有已识别畸变进行编目并精确描述，对于改进预防不稳定性的方法和确保遗传质量控制至关重要。我们报告了对来自33名个体的皮肤成纤维细胞、尿沉渣和外周血单个核细胞的65个细胞系的核型分析，其中82%的个体患有与遗传不稳定无关的单基因遗传疾病。20号和8号染色体三体反复出现，而1q臂是最常受影响的区域，涉及与15号和18号染色体的间质性重复和不平衡易位。通过SNP阵列确定的重排断点在大基因和组蛋白基因簇中的定位，将iPSC中的遗传不稳定与常见和早期复制的脆性位点处复制应激诱导的染色体断裂联系起来。
