Circadian rhythms in stem cell biology and function

Abstract

The mammalian circadian clock is a time-keeping system that adapts the body physiology to light/dark cycles with a period of 24 hours. It consists of a central clock in the suprachiasmatic nucleus (SCN) within the brain, and peripheral clocks in multiple other tissues. While the central clock is entrained by light, peripheral clocks are kept in synchrony by the SCN via humoral factors, metabolites and body temperature. Additionally, SCN independent determinants like food and physical activity influence peripheral clocks that can therefore oscillate in a cell-autonomous manner. The circadian clock has been implicated in various processes such as cell cycle, cell differentiation, metabolism, aging, and regeneration. Indeed, impairment of the clock leads to defects ranging from sleep, metabolic and cardiovascular disorders to premature aging and even the development of cancer. Concerning cardiac regenerative therapy, stem cells show a tremendous potential to improve heart function after impairment. Interestingly, the circadian clock modulates stem cell dormancy, mobilization and proliferation. In this chapter we review the function of circadian rhythms in stem cells and their derivatives. We outline their implication in regeneration, with a focus on how the circadian clock influences myocardial biology and how it might improve cardiac therapy.