Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Turin, Italy.
McMaster Stem Cell and Cancer Research Institute, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
Int J Mol Sci. 2017 Sep 13;18(9):1952. doi: 10.3390/ijms18091952.
Evaluation of the extent and nature of induced pluripotent stem cell (iPSC) genetic instability is important for both basic research and future clinical use. As previously demonstrated regarding embryonic stem cells, such DNA aberrations might affect the differentiation capacity of the cells and increase their tumorigenicity. Here, we first focus on the contribution of multiple DNA damage response pathways during cellular reprogramming. We then discuss the origin and mechanisms responsible for the modification of genetic material in iPSCs (pre-existing variations in somatic cells, mutations induced by reprogramming factors, and mutations induced by culture expansion) and deepen the possible functional consequences of genetic variations in these cells. Lastly, we present some recent improvements of iPSC generation methods aimed at obtaining cells with fewer genetic variations.
评估诱导多能干细胞（iPSC）遗传不稳定性的程度和性质对于基础研究和未来的临床应用都很重要。正如之前在胚胎干细胞中所证明的那样，这种 DNA 异常可能会影响细胞的分化能力并增加其致瘤性。在这里，我们首先关注在细胞重编程过程中多种 DNA 损伤反应途径的贡献。然后，我们讨论了 iPSCs 中遗传物质修饰的来源和机制（体细胞中预先存在的变异、重编程因子诱导的突变以及培养扩增诱导的突变），并深入探讨了这些细胞中遗传变异的可能功能后果。最后，我们介绍了一些最近改进的 iPSC 生成方法，旨在获得遗传变异较少的细胞。
