Figure 4. Integrating stem cell function with systemic physiology.

Physiological changes experienced by animals cause changes in stem cell function that lead to adaptive changes in tissue growth and remodeling. Stem cell function is modulated by long-range extrinsic signals that reflect changes in nutrition (A), circadian regulation (B), hormones (C, D), and oxygen tension (E). These signals sometimes act directly on stem cells and sometimes act on niche cells to indirectly modulate stem cell function (see text for details and references). The CNS is integral to the coordination of many physiological changes through neural activity (B) and the secretion of hormones (D). A. Stem cell function is modulated by insulin and other signals that reflect nutritional status. B. Stem cells are regulated by circadian rhythms generated centrally in the suprachiasmatic nucleus (SCN) of the brain and conveyed through the sympathetic nervous system (SNS). C, D. Sexual maturation, mating, and pregnancy can influence stem cell function by changing the expression of hormones from the gonads (C) and the pituitary gland (D). E. Physiological changes also modulate stem cell function by altering oxygen levels and systemic levels of cytokines and growth factors in the blood. Dashed arrows indicate factors secreted from the indicated organ that act on stem cells and their niches in multiple target tissues (green and orange).