Figure 8.

The intrinsic timetable model of stem cell biology. In this model, the functional properties of stem cells are (i) linked to the number of preceding cell divisions or generations (g) and (ii) unevenly distributed among daughter cells upon each cell division. It is postulated that each stem cell division is asymmetric and results in daughter cells that differ in cell cycle properties. As a result, the time interval between successive generations (t 1, t 2, etc.) is variable between clones of the same generation and the interval between divisions is subject to both intrinsic (developmental) and extrinsic (microenvironment and growth factors) control. Clonal variations in turn-over time result in an extreme hierarchy of stem cells varying in replicative history and related functional properties that is difficult to reconcile with the concept of stem cells as a homogeneous population of cells.