CGH analysis of mouse embryonic stem cells trisomic for chromosome 6, 8, 11,12 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. Array comparative genomic hybridization (aCGH) was performed to detect the DNA copy number variants of the trisomic mES cells on a genome-wide scale. For Ts6, Ts8, Ts11 and Ts15 ES cells, we used the wild-type AB1 mES cells (129 S7/SvEvBrd, male) as reference. For Ts8-JM8 and Ts12-JM8 ES cells, we usedJM8A3 mES cells (C57BL/6N, male) as reference. The copy number variants of all the cell lines were analyzed by NimbleGen Mouse CGH 3x720K Whole-Genome Tiling Arrays (Build MM9) with an average probe spacing of 3.5 kb.