Recurrent trisomy and Robertsonian translocation of chromosome 14 in murine iPS cell lines.
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.
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China.
Qian
Q
Chen
Xiaoyun
X
Shi
Cornelia
C
Rudolph
Yong
Y
Yu
Ding
D
Zhang
Xiaoyu
X
Zhao
Sabine
S
Mai
Gang
G
Wang
Brigitte
B
Schlegelberger
Qinghua
Q
Shi
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002871:Chromosome Banding; D002875:Chromosomes / Q000737:chemistry / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059785:Karyotype; D007621:Karyotyping / Q000379:methods*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism / Q000494:pharmacology; D014178:Translocation, Genetic; D014314:Trisomy
C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc