Inter-layer and inter-subject variability of circadian gene expression in human skin

This work reports 24 h gene expression rhythms in two skin layers, epidermis and dermis, in a cohort of young, healthy adults, who maintained natural, regular sleep-wake schedules. 10% of the expressed genes showed such diurnal rhythms at the population level, of which only a third differed between the two layers. Amplitude and phases of diurnal gene expression varied more across subjects than layers, with amplitude being more variable than phases. Expression amplitudes in the epidermis were larger and more subject-variable, while they were smaller and more consistent in the dermis. Core clock gene expression was similar across layers at the population-level, but were heterogeneous in their variability across subjects. This work provides a valuable resource to advance our understanding of human skin and presents a novel methodology to quantify sources of variability in human circadian rhythms. To analyze diurnal gene expression in human dermis and epidermis, eleven different young and healthy adults who maintained their natural, regular sleep schedules were biopsied from the upper back every 4 h for 1 full day and whole genome microarray analysis was performed. We used this data to quantify variability in rhythm parameters across skin layers and individuals, and to identify small sets of biomarker genes for internal clock phase in each layer.