Aneuploidy in immortalized human mesenchymal stem cells with non-random loss of chromosome 13 in culture.
Aneuploidy (an abnormal number of chromosomes) is commonly observed in most human cancer cells, highlighting the need to examine chromosomal instability in tumorigenesis. Previously, the immortalized human mesenchymal stem cell line UE6E7T-3 was shown to undergo a preferential loss of one copy of chromosome 13 after prolonged culture. Here, the loss of chromosome 13 was found to be caused by chromosome missegregation during mitosis, which involved unequal segregation, exclusion of the misaligned chromosome 13 on the metaphase plate, and trapping of chromosome 13 in the midbody region, as observed by fluorescence in situ hybridization. Near-diploid aneuploidy, not tetraploidy, was the direct result. The loss of chromosome 13 was non-random, and was detected by analysis of microsatellites and single nucleotide polymorphism-based loss of heterozygosity (LOH). Of the five microsatellite loci on chromosome 13, four loci showed microsatellite instability at an early stage in culture, and LOH was apparent at a late stage in culture. These results suggest that the microsatellite mutations cause changes in centromere integrity provoking loss of this chromosome in the UE6E7T-3 cell line. Thus, these results support the use of this cell line as a useful model for understanding the mechanism of aneuploid formation in cell cultures.
Takeuchi
Masao
M
Division of Bioresources, National Institute of Biomedical Innovation, Osaka, 567-0085, Japan. takeuchim@nibio.go.jp
Takeuchi
Kikuko
K
Ozawa
Yutaka
Y
Kohara
Akihiro
A
Mizusawa
Hiroshi
H
D000782:Aneuploidy; D002461:Cell Line, Transformed; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D004171:Diploidy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008938:Mitosis; D013997:Time Factors