Figure 1.

Cell Behavior in Mouse Esophageal Epithelium

(A) Cartoon showing the mouse esophageal epithelium structure. Progenitor cells in the basal layer divide to generate progenitor and differentiating daughter cells. The latter subsequently exit the cell cycle and migrate out of the basal layer through the suprabasal cell layers to the epithelial surface from which they are shed. Progenitor division may generate two progenitors, two differentiated cells, or one of each cell type. The probabilities of each symmetric division outcome (indicated by percentages) are balanced so that, on average, across the basal layer, each division generates 50% progenitors and 50% differentiating cells.

(B) Clonal dynamics. The behavior of progenitors results in most cells that acquire a neutral mutation being lost by differentiation and shedding within a few rounds of division (left clone). Only a few clones will expand to a size that means they are likely to persist long term (right clone).

(C) Positively selected mutants tilt the normally balanced average division outcome toward proliferation, increasing the proportion of persisting mutant clones, whereas a negatively selected mutation that tilts fate toward differentiation will be depleted from the tissue because an increased proportion of clones will be lost by shedding.