It is hypothesized that OCT4, NANOG, KLF4 and SOX2 form extensive feed-forward and feedback loops to organize a stem-cell-like transcriptional enhancer circuitry in ESCs, which could also be mechanistically responsible for inducing stem cell-like characteristics, block expression of differentiation genes, and increase cellular heterogeneity of cancer cells. The gene discussed is POU5F1; the disease is cancer.