Figure 2.
The epigenetic landscape metaphor for cell transformation. The model presents a progenitor/tissue stem cell with an early multipotent phenotype and self-renewal capacity (circular arrow), as determined by the expression state/profile of a host of genes within a developmental gene network (X1, X2, X3, …, Xn), which is represented by the horizontal plane below the landscape. Three example genes within the larger network are shown, as they might appear at a particular stage of cell development. The gene regulatory interactions are the “forces” that shape the hills and valleys in the epigenetic landscape, propelling the progenitor toward development while constraining transitions among available phenotypes to particular channels (green arrows indicate normal progression toward separate developmental fates). A series of gene network states, with changes in expression of its individual genes, determine the topography of the development landscape. In this model, cell transformation is depicted as a diversion from the predetermined developmental channels, where self-renewal capacity is greatly diminished, into gene network expression states that create alternate, immature phenotypes with limited developmental potential and increased and perpetual self-renewal capacity (red arrows indicate abnormal progression due to transformation events).