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. Author manuscript; available in PMC: 2014 Apr 11.
Published in final edited form as: Oncogene. 2012 Jul 2;32(15):1869–1875. doi: 10.1038/onc.2012.281

Figure 3. The Goldilocks Rule for stem cells.

Figure 3

A. Young healthy stem cells are proposed to possess parameters (cell cycle, differentiation, interactions with the niche, etc.) that are near optimal (“just right”) for maintenance as a stem cells. Stem cells are presumed to occupy a local fitness peak on the adaptive landscape; cancer cells in the same tissue could occupy a higher peak, but transitions to this peak would require passage through lower fitness states on the landscape (see (36)). Thus, acquisition of a single oncogenic mutation would typically be disadvantageous, by changing parameters from their optimum (see Table 1). B. For old or damaged stem cells, parameters are suboptimal or abnormal, and the stem cells no longer possess optimal or near optimal fitness. Changes in parameters could result from both cell-autonomous events (damage to the stem cells) or from non-cell autonomous changes (such as degradation of the niche or systemic changes). These changes in the stem cell pool can lead to selection for oncogenic events that are adaptive to this context.