In the case of osteosarcoma, since the dedifferentiation of p53- or/and Rb-deficient mature osteoblasts underlies their malignant transformation4, 11, 12, 13, it is not surprising to find that SSEA-4− osteosarcoma cells retain the capacity to dedifferentiate, thus regenerating SSEA-4+ TICs. The gene discussed is RB1; the disease is osteosarcoma.