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Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12313-12318. doi: 10.1073/pnas.1809442115. Epub 2018 Oct 30.

Population-level rhythms in human skin with implications for circadian medicine.

Author information

1
Division of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
2
Division of Pediatric Otolaryngology and Pulmonary and Sleep Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
3
Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati School of Medicine, Cincinnati, OH 45267.
4
Department of Medicine, Center for Sleep and Circadian Neurobiology, Institute for Biomedical Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
5
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37203.
6
Procter & Gamble Company, Mason, OH 45040.
7
Division of Human Genetics and Immunobiology, Center for Chronobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; john.hogenesch@cchmc.org.

Abstract

Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. The epidermal layer shows rhythmic physiological responses to daily environmental variation (e.g., DNA repair). We investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, in which a limited set of human subjects (n = 20) were sampled throughout the 24-h cycle and a larger population (n = 219) were sampled once. We found a robust circadian oscillator in human epidermis at the population level using pairwise correlations of clock and clock-associated genes in 298 epidermis samples. We then used CYCLOPS to reconstruct the temporal order of all samples, and identified hundreds of rhythmically expressed genes at the population level in human epidermis. We compared these results with published time-series skin data from mice and found a strong concordance in circadian phase across species for both transcripts and pathways. Furthermore, like blood, epidermis is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human epidermis that is capable of reporting circadian phase to within 3 hours from a single sample. In summary, we show rhythms in human epidermis that persist at the population scale and describe a path to develop robust single-sample circadian biomarkers.

KEYWORDS:

biomarkers; circadian medicine; human skin; hybrid design; population-level rhythms

PMID:
30377266
PMCID:
PMC6275491
[Available on 2019-05-27]
DOI:
10.1073/pnas.1809442115

Conflict of interest statement

Conflict of interest statement: K.J.M., J.E.O., J.D.S., and R.T. are employees of the Procter & Gamble Company, which markets skin care products.

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