Fig. 1

p53 is a switch in embryonic stem cells. Reversible transitions between differentiated cells and embryonic stem cells (ESCs) can occur when p53 is switched off. The protein p53 separates differentiated cells from ESCs when the p53 switch is on. a Under normal conditions, with an intact p53 signaling pathway, ESCs can differentiate when culture conditions are shifted from mouse ESC (mESC) medium containing leukemia inhibitory factor (Lif) for mouse ESCs to mouse embryonic fibroblast (mEF) medium supplemented with retinoic acid (RA). The differentiation process is depicted as cells differentiating from the top to the bottom of the developmental hill. A differentiated cell that has crossed an intact p53 shield cannot return to the top of this hill, which is in the pluripotent stem cell state. b Conversely, without p53 (as showed in the figure, the p53 is far from the system and the developmental hill is compressed) differentiated cells can be easily reprogrammed to pluripotent ESCs. For example, differentiated cells can be de-differentiated or reprogrammed to ESCs when the p53 switch is off in humanized p53S315A knock-in mouse ESCs as reported in our previous study [24]