Pharmacological modulation of H3K9me2 deposition in human intestinal models and transformed ES cells

Transformed variant of H9 human ES cells (t-hESC) represent a surrogate model for cancer stem cells in adherent cultures, which faithfully recapitulate the main functional, transcriptional, and epigenetic characteristics of CSCs in culture and in vivo. The use of G9a inhibitor BIX-01294 reduced the levels of H3K9me2 and global DNA methylation in t-hESCs. Thus, we performed transcriptome-profiling experiments on control and BIX-treated t-hESC to study the impact of G9a inhibition on gene networks associated with neoplastic stemness. Moreover, using a phenotypic chemical screening assay, we identified vanoxerine (YB-1471) as a new small molecule decreasing H3K9me2 deposition in t-hESCs. In addition to t-hESCs, transcriptome profiling was performed normal human intestinal epithelial crypt (HIEC) cells and colorectal cancer cell line HT29 upon treatment with vanoxerine. Whole transcriptome profiling.