Effects of the histone acetylase inhibitor C646 on growth and differentiation of adipose-derived stem cells

Abstract

ABSTRACT As an important histone acetylase, the transcriptional coactivator P300/CBP affects target gene expression and plays a role in the maintenance of stem cell characteristics and differentiation potential. In this study, we explored the action of a highly effective selective histone acetylase inhibitor, C646, on goat adipose-derived stem cells (gADSCs), and investigated the impact of histone acetylation on the growth characteristics and the differentiation potential of ADSCs. We found that C646 blocked the cell proliferation, arrested the cell cycle, and triggered apoptosis. Notably, immunocytochemistry and western blot analyses showed that the acetylation level of histone H3K9 was increased. Moreover, although real-time quantitative PCR and western blot confirmed that P300 expression was inhibited under these conditions, the expression level of two other histone acetylases, TIP60 and PCAF, was significantly increased. Furthermore, C646 clearly promoted the differentiation of gADSCs into adipocytes and had an impact on their differentiation into neuronal cells. This study provides new insights into the epigenetic regulation of stem cell differentiation and may represent an experimental basis for the comprehension of stem cell characteristics and function. Furthermore, it is of great relevance for the application of adult stem cells to somatic cell cloning, which may improve the efficiency of large livestock cloning and foster the production of transgenic animals.