Gene expression in mouse embryonic stem cells trisomic for chromosome 6, 8, 11 and 15

Aneuploidy, an uneven number of chromosomes, leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem cells. Using a novel genetic scheme, we generated a series of aneuploid cell lines that each carries an extra copy of single chromosomes and then characterized the traits shared by these cell lines. All the aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self-renewal and showed a reduced capacity to differentiate in vitro. Moreover, xenografted aneuploid stem cells formed teratomas more efficiently, with features of neoplastic progression. These findings demonstrate that aneuploidy enhances the self-renewal capacities of stem cells and reduces their differentiation abilities. We used the wild-type AB1 mouse ES cells (male) as control. The mouse ES cell lines with three copies of chromosome 6, 8, 11 or 15 were the experimental samples. Two biological replicates were used for each cell line. The samples were: WT (P18 and P20), Ts6 (P9 and P18), Ts8 (P10 and P13), Ts11 (P8 and P11), Ts15 (P11 and P14). Gene expression profiles of all the cell lines were analyzed on the Agilent SurePrint G3 Mouse Gene Expression 8×60 K microarrays. They include probes to mRNAs and long intergenic non-coding RNAs (lincRNAs).