Peripheral timekeeping: Mammalian cells outside the brain have their own circadian clocks

Researchers have discovered that individual fibroblast cells contain independent, self-sustaining circadian (ca. 24 hr) clocks. Circadian clocks are important for synchronizing many physiological and behavioral processes to the day/night cycle.

For decades it has been known that a tiny cluster of brain cells known as the suprachiasmatic nucleus (SCN) is required for expression of circadian rhythms in mammals. When clock genes were identified in the late ’90s, they were found to be expressed rhythmically not only in SCN but also in many other tissues. Some of these studies used the firefly luciferase gene, introduced into cells with regulatory elements from a clock gene, so that cell cultures emitted light with a circadian rhythm. However, peripheral tissue rhythms tended diminish after a few cycles in culture, suggesting that they might depend on the central nervous system’s SCN to drive them.

In the new work, performed by researchers at The Scripps Research Institute and Northwestern University, Dr. David Welsh and colleagues used bioluminescence imaging to monitor circadian rhythms of clock gene expression from individual rat or mouse fibroblasts. Robust rhythms of single cells persisted without diminishing for at least 1–2 weeks in culture. Cells were partially synchronized by medium change at the start of an experiment, but because of different circadian periods drifted out of phase after several days, leading the ensemble rhythm to diminish. Thus, even cells outside the brain contain bona fide circadian clocks.