Replicative cellular age distributions in compartmentalized tissues
Abstract
The cellular age distribution of hierarchically organized tissues can reveal important insights into the dynamics of cell differentiation and self-renewal and associated cancer risks. Here, we examine the effect of progenitor compartments with varying differentiation and self-renewal capacities on the resulting observable distributions of replicative cellular ages. We find that strongly amplifying progenitor compartments, i.e. compartments with high self-renewal capacities, substantially broaden the age distributions which become skewed towards younger cells with a long tail of few old cells. For several of these strongly amplifying compartments, the age distribution becomes virtually independent of the influx from the stem cell compartment. By contrast, if tissues are organized into many downstream compartments with low self-renewal capacity, the shape of the replicative cell distribution in more differentiated compartments is dominated by stem cell dynamics with little added variation. In the limiting case of a strict binary differentiation tree without self-renewal, the shape of the output distribution becomes indistinguishable from that of the input distribution. Our results suggest that a comparison of cellular age distrib...Continue Reading
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