Transcriptional profilling of hESC with and without 17q gain upon induction of replicative stress through HU treatment [RNA-Seq]

Human embryonic stem cells (hESC) and cancer cells rapidly divide with a short G1/S-phase causing increased replicative stress (RS). Since both in vitro cultured hESCs and most high-risk neuroblastomas have large chromosome 17q gains (17q+), we hypothesize that this may provide a "RS-resistance phenotype". We co-cultured parental cells and a derived hESC line with 17q+ under normal growth conditions and under RS. We could show a proliferative ad-vantage of hESC with 13q+17q+ over wild type by measurement of the cumulative growth and molecular analysis for chromosomal copy number analysis. To monitor effects of 17q+ on RS-resistance, cell cycle and transcriptome analysis were performed. In conclusion, we show that extra chromosomal aberrations, such as 17q+, provide proliferative advantage to hESC under RS and suggest that this phenomenon explains the high incidence of 17q+ in in vitro cultured hESC lines. Samples were collected at 6 consecutive splitting moments of hESC with and without 17q gain, under normal growth conditions (PBS) or conditions of replicative stress (150 µM HU), for 2 biological replicates