Extended Data Fig. 1: Architecture and dynamics of murine esophageal epithelium.

(a) H&E images and schematic of the mouse esophageal epithelium architecture and dynamics; b = basal cell layer (delineated by white dots), sb = suprabasal layers, str = stroma. Scale-bars: 500µm (left image), 50µm (inset). Dividing (progenitor) cells are confined to the basal layer. Differentiating cells exit the cell cycle, migrate out of the basal layer, through the suprabasal layers, and are finally shed into the lumen. (b–c) The single progenitor model (see Supplementary Note). All progenitor cells in the basal layer are functionally equivalent and following division produce either: two progenitors that will persist in the tissue, two differentiating cells that will cease division, stratify and be lost, or one cell of each type. In homeostasis (b), the likelihood of the two progenitor and two differentiating cell outcomes is equal. Mutations (c) may tip the balance towards a non-neutral behavior, resulting in clonal growth if they favor proliferation of daughter cells. (d) Expansion of mutant clones is defined by their relative competitive fitness to adjacent clones. Initially, a fit “winner” mutant progenitor (colored) shows a fate bias towards proliferation and outcompetes its less fit “loser” surrounding cells, resulting in clonal expansion. Eventually, mutant clones begin to collide with each other until surrounded by similarly competitive mutants, at which point their cell fate reverts towards balance and their expansion slows (see Supplementary Note).