Nevertheless, the upregulation of RUNX2 (Supplementary Fig. 4g) but not of OCN mRNA levels or ALP activity could be caused by S6K knockdown (Supplementary Fig. 4j), thus indicating that SSEA-4− osteosarcoma cells are a heterogeneous population lying at discrete differentiation stages, and that S6K inhibition alone promoted only an osteogenic commitment of SSEA-4+ TICs but not further maturation. Here, RPS6KB1 is linked to osteosarcoma.