Designing and Evaluating Circadian Experiments on Mouse Skin

All skin layers and cutaneous appendages harbor a robust circadian clock, whose phase is under the influence of light through the central clock in the suprachiasmatic nucleus. The skin clock coordinates fundamental biological processes, including metabolism and stem cell activation. It also prominently modulates activity of skin-resident immune cells and the inflammatory response. Numerous diurnally regulated genes in the skin have been implicated in skin diseases in GWASs. Therefore, the mouse skin is a powerful model for understanding the diverse roles of circadian biology in maintaining tissue health and the initiation and propagation of disease states. When planning experiments to study the circadian biology of mouse skin, multiple technical and biological factors must be carefully considered. In this paper, we provide comprehensive guidance on the general circadian experimental design and associated housing for the mice. We highlight the importance of aligning sample collection with the desired hair cycle stage and animal age. We introduce methods to disrupt the clock in the skin, including altering light and feeding schedules as well as using transgenic mouse models. Finally, we discuss the use of transcriptomic data, both bulk and single cell, for circadian studies.