Apart from EMT, differentiated cancer cells have been largely reported to be directly reprogrammed to CSCs by extracellular cues from the tumor microenvironment including hypoxia, ROS, and cytokines [7,8], as well as by ectopic expression of pluripotent transcriptional factors OCT3/4, SOX2, KLF4, and cMYC [9]. The gene discussed is POU5F1; the disease is cancer.