Nested cells represent a unique cellular subpopulation capable of binary differentiation: on one hand, they maintain the condition of cancer stem cell in a small fraction (probably via multinucleation) as seen by the expression of stem cell markers like Oct-4, SOX2 and Klf-4 and, on the other hand, they differentiate towards an epithelial condition as seen by gradual loss of mesenchymal characteristics in parallel with the acquisition of the epithelial phenotype, thus shaping the cellular heterogeneity present in tumors (Fig. 5, Panel D, SF10). This evidence concerns the gene POU5F1 and cancer.