  How can tissues generate large numbers of cells, yet keep the divisional load
(the number of divisions along cell lineages) low in order to curtail the
accumulation of somatic mutations and reduce the risk of cancer? To answer the
question we consider a general model of hierarchically organized self-renewing
tissues and show that the lifetime divisional load of such a tissue is
independent of the details of the cell differentiation processes, and depends
only on two structural and two dynamical parameters. Our results demonstrate
that a strict analytical relationship exists between two seemingly disparate
characteristics of self-renewing tissues: divisional load and tissue
organization. Most remarkably, we find that a sufficient number of
progressively slower dividing cell types can be almost as efficient in
minimizing the divisional load, as non-renewing tissues. We argue that one of
the main functions of tissue-specific stem cells and differentiation
hierarchies is the prevention of cancer.
