Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China.
Chromosome Res. 2011 Oct;19(7):857-68. doi: 10.1007/s10577-011-9239-y. Epub 2011 Oct 19.
Induced pluripotent stem (iPS) cells have greatly provoked people's interest due to their enormous potential of clinical applications. Increasing care is taken with the genetic safety of iPS cells. However, up to now, the chromosomal integrity of murine iPS (miPS) cells has been largely unknown. We have observed recurrent trisomy and/or Robertsonian translocation (Rb) of chromosome 14 in six out of nine independent miPS cell lines from three laboratories by G-banding, fluorescence in situ hybridization (FISH) and spectral karyotyping (SKY) analyses, while all the miPS cell lines were derived from mouse embryonic fibroblasts (MEFs) or neural precursor cells (NPCs) with a normal karyotype. The miPS cells with trisomy and/or Rb of chromosome 14 showed growth advantage over the miPS cells with a normal karyotype. We found a significantly higher frequency of Rbs in the miPS cell lines induced with c-Myc than those without c-Myc. Our findings demonstrate that miPS cell lines have the propensity for chromosomal aberrations and there is an obvious correlation between the extent of chromosomal aberrations in miPS cells and the transcriptional factors used for their reprogramming. Therefore, our study raises awareness of the need for improvements of the induction conditions of miPS cells in order to avoid the chromosomal aberrations and ensure future safe applications.
诱导多能干细胞（iPS 细胞）由于其巨大的临床应用潜力而引起了人们的极大兴趣。人们越来越关注 iPS 细胞的遗传安全性。然而，到目前为止，还不清楚鼠源 iPS（miPS）细胞的染色体完整性。通过 G 带、荧光原位杂交（FISH）和光谱核型分析（SKY）分析，我们在来自三个实验室的九种独立的 miPS 细胞系中的六种中观察到染色体 14 的反复三体和/或罗伯逊易位（Rb），而所有的 miPS 细胞系均源自具有正常核型的小鼠胚胎成纤维细胞（MEFs）或神经前体细胞（NPCs）。与具有正常核型的 miPS 细胞相比，具有染色体 14 三体和/或 Rb 的 miPS 细胞表现出生长优势。我们发现，在用 c-Myc 诱导的 miPS 细胞系中，Rb 的频率明显高于没有 c-Myc 的细胞系。我们的研究结果表明，miPS 细胞系容易发生染色体异常，miPS 细胞中的染色体异常程度与用于其重编程的转录因子之间存在明显的相关性。因此，我们的研究提醒人们需要改进 miPS 细胞的诱导条件，以避免染色体异常，并确保未来安全应用。
