  Cycling tissues such as the intestinal epithelium, germ line, and hair
follicles, require a constant flux of differentiated cells. These tissues are
maintained by a population of stem cells, which generate differentiated
progenies and self-renew. Asymmetric division of each stem cell into one stem
cell and one differentiated cell can accomplish both tasks. However, in
mammalian cycling tissues, some stem cells divide symmetrically into two
differentiated cells and are replaced by a neighbor that divides symmetrically
into two stem cells. Besides this heterogeneity in fate (population asymmetry),
stem cells also exhibit heterogenous proliferation-rates; in the long run,
however, all stem cells proliferate at the same average rate (equipotency). We
construct and simulate a mathematical model based on these experimental
observations. We show that the complex steady-state dynamics of
population-asymmetric stem cells reduces the rate of replicative aging of the
tissue --potentially lowering the incidence of somatic mutations and genetics
diseases such as cancer. Essentially, slow-dividing stem cells proliferate and
purge the population of the fast-dividing --older-- cells which had undertaken
the majority of the tissue-generation burden. As the number of slow-dividing
cells grows, their proliferation-rate increases, eventually turning them into
fast-dividers, which are themselves replaced by newly emerging slow-dividers.
Going beyond current experiments, we propose a mechanism for equipotency that
can potentially halve the rate of replicative aging. Our results highlight the
importance of a population-level understanding of stem cells, and may explain
the prevalence of population asymmetry in a wide variety of cycling tissues.
