Figure 1.

Conrad Waddington likened cell fate to a marble rolling downhill into one of several troughs representing fully differentiated cell types. Nuclear transfer and reprogramming showed that cells can be rolled back to the top of the hill by epigenetically altering the cell. Now, it is clear that cells can travel part way up the hill to roll back down a discrete number of troughs or even travel from one trough to another without going back up the hill at all, although the epigenetic barriers for such travel appear greater than traveling up hill.