The crypt cycle and the asymptotic dynamics of the proportion of differently sized mutant crypt clones in the mouse intestine

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Abstract
The dynamics of clones of intestinal epithelial crypts populated by mutant stem cells offers the hope of new and independent evidence of continued crypt replication throughout adult life, an important prediction of recent models of intestinal stem cell biology. It is shown here that the experimentally most tractable measurement--scoring of the fraction of groups of mutant crypts found as isolated singletons, pairs, or clusters of > or = 3 mutant crypts--should tend to an asymptotic distribution as animals age. In particular, if the rate of mutation is low relative to the rate of crypt production then 1/2, 1/6 and 1/3 of groups of mutant crypts should be found as singletons, pairs, and larger clusters, respectively, as animals reach old age. Such a result is not immediately obvious, and if obtained from an experiment could easily be misinterpreted as implying that the crypt cycle must slow radically as animals age.