Trisomy 12 in HESC leads to no selective in vivo growth advantage in teratomas, but induces an increased abundance of renal development

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Abstract
The aim of this investigation was to examine the impact of chromosome 12 amplification (tri-12 cells) in human embryonic stem cells (HESC), following in vivo engraftment to an immunodeficient xeno-model. For this we used sublines from the HESC line HS181, spontaneously exhibiting either low or high frequencies of tri-12 cells. Fluorescent in situ hybridization (FISH) analysis revealed a random distribution of tri-12 cells in the HS181 colonies in vitro. Similarly, the contribution of tri-12 cells to the development of various tissues in teratomas in vivo seemed to be fully random with no particular preference regarding in vivo differentiation pathway of tri-12 HS181 cells compared to HS181 cells with disomy 12 (di-12 cells). On the other hand, following in vivo transplantation the ratio of tri-12/di-12 cells was significantly reduced (P < 0.001), indicating a negative selection for this trisomy in vivo. Moreover, injection of HS181 cultures containing tri-12 cells resulted in a significantly increased abundance of areas compatible with renal formation (P < 0.001), relative teratomas derived from injection of di-12 HS181 cells. However, such areas included no increased relative frequency of tri-12 cells, suggesting indirect mechanism(s) for the increased abundance of renal development. The reasons for such developmental bias are unknown and warrant further investigation. J. Cell. Biochem. 100: 1518–1525, 2007.