Fig. 7: The figure shows the possible ways of cell development: transdifferentiation, reprogramming and natural development. (Graphic reproduced by kind permission of Stem Cell Network.NRW)

The possibility of transdifferentiation and reprogramming of cells (see module “Reprogramming of cells” in this “In Focus”) questions a concept that has served for decades as a model to illustrate the progressive restriction of cell differentiation potential during normal development: the so-called “epigenetic landscape” of the British developmental biologist Conrad H. Waddington. The differentiation path of a cell, also called cell fate, is illustrated in Waddington’s model by a marble that rolls down a mountain landscape, which is divided into several valleys (see Fig. 8). Each valley stands for a specific differentiated cell type. Traditionally, it was assumed that the path of a cell was unidirectional, that means only possible in one way, and irreversible. The possibility of reprogramming of cells, however, shows that one can reverse the path of the cell. The transdifferentiation, in turn, allows it to get directly from one valley to the next. The emergence of these techniques suggests that somatic and pluripotent cell fates can be interconverted without transiting through distinct hierarchies as described by Waddington.