Controls on the cell cycle.

The control of cell proliferation, in physiological terms, depends not so much on our understanding of the sequence of biochemical events unfolding as a cell progresses through its proliferation cycle, as upon the recognition by a tissue of the demands for functional cells of a particular type. After considering the modes of control possible, i.e. by recruitment of resting G0-state cells into cycle or by modifying the proliferative behaviour of already proliferating cells, haemopoietic tissue is used as a model to illustrate how the principles of proliferation control in specific cell lineages can be effected. Although the mode of stem cell control is different from that in the maturing populations, all depend on a co-ordination of negative feedback loops for inhibitor and stimulator which are specific to that cell population. The concept of a 'quantal' cell cycle is considered but its application to control in an adult steady-state tissue must be modified to take account of microenvironmental influences which are shown, by their cellular organization, to be an important feature in haemopoietic and probably all other tissues.