Induction of differentiation of pluripotent stem cells by Aurora-B kinase inhibitor

Human pluripotent stem cells (hPSCs) combine the features of robust proliferation with precise differentiation capacity. The molecular mechanisms orchestrating the differentiation process are poorly understood. In a previous shRNA screen, Aurora-B, the enzymatic component of the chromosomal passenger complex (CPC), has been identified as a candidate involved in pluripotency of mouse PSCs. Here we show that inhibition of Aurora-B kinase activity results in spontaneous differentiation of hPSCs. Sustained Aurora-B kinase activity results from the stabilization of the CPC components Aurora-B and Borealin due to low APC/CCdh1 activity in hPSCs. During hPSC differentiation, CPC activity is terminated by activated APC/CCdh1. RNA-seq analysis reveals that CPC activity maintained the epithelial characteristics of hPSCs via inhibition of an epithelial-to-mesenchymal transition (EMT) program. In conclusion, sustained CPC activity plays a critical role in the maintenance of pluripotency. We therefore propose an interphase role of the CPC in regulating embryonic pluripotency.