With the pre-festive season and the long winter darkness that accompanies it, it is appropriate to wonder how daylight/darkness cycles affect our biology. Regular daily variations such as daylight/darkness cycles are called circadian rhythms. For example, human skin needs to respond to harmful UV radiation generated by sunlight in a circadian manner. Amazingly, our cells have developed an inherent and self-sustained clock in order to adapt their behavior to these daily fluctuations.
In a recent study published in Cell Stem Cell, Janich and colleagues tried to understand how circadian rhythms could modulate self-renewal and differentiation of human skin (epidermal) stem cells. Part of their approach consisted in using genetic engineering to increase and sustain the expression of the core clock genes Per1 and Per2, core clock genes being required for regulation of circadian rhythms in cells. They show that this over-expression of Per1 and Per2 results in spontaneous stem cell differentiation.
In this picture, one can observe skin that is obtained from the transplantation of a mixture of human skin stem cells (in red and in green, transplanted at 1:1 ratio in the 3 panels) into recipient mice. In all three panels, the red cells are “normal” cells. In the control left panel, the green cells are also “normal” (EV). One can see that the bottom (basal) layer, the one in which the stem cells reside, is composed of green and red cells. In the middle panel, the green cells have been engineered to over-express Per1. In the right panel, the green cells over-express Per2. In contrast to the left panel, the green cells that over-express Per1 or Per2 are found in the upper skin layers (differentiated cells) and not in the basal layer containing the stem cells. From this observation, the authors conclude that over-expression of the core clock genes Per1 or Per2 triggers epidermal stem cell differentiation.
This example shows that circadian rhythms play important roles in stem cell decisions. Interestingly, it has also been shown in another study that strong disturbance of circadian rhythms can lead to premature ageing. So while you enjoy your Christmas holidays, make sure you get your beauty sleep, your stem cells need it!
Janich, P., Toufighi, K., Solanas, G., Luis, N. M., Minkwitz, S., Serrano, L., Lehner, B. and Benitah, S. A. (2013) ‘Human epidermal stem cell function is regulated by circadian oscillations’, Cell Stem Cell 13(6): 745-53.