REGULATION OF TRANSCRIPT SPLICING BY SON IN EMBRYONIC STEM CELLS

Abstract

Human embryonic stem cells (ES) have the ability to differentiate into clinically relevant cell types. In the maintenance of human ES cell pluripotency, both transcription factors and epigenetic modifiers have been demonstrated to play essential roles. However, there is scarce knowledge about the regulation of pluripotency through transcript splicing. In this study, we aim to examine the function of the spliceosome-associated factor SON in human ES cells. We show that SON is upregulated in human ES cells as compared to differentiated cells. In addition, SON is important for both the maintenance and induction of pluripotency in human ES cells and MRC-5 fibroblasts, respectively. Depletion of SON leads to apoptosis and loss of pluripotency in human ES cells. Moreover, we identified SON-regulated transcripts by performing genome-wide RNA profiling. Importantly, we confirmed that SON binds to transcripts encoding pluripotency regulators and regulates their splicing in human ES cells. Together, our results establish a link between splicing regulation of transcript production to self-renewal and pluripotency of human ES cells.