UC Irvine

The circadian clock, a transcription-translation feedback loop responsible for generating robust rhythms that are roughly synchronized to the external 24-hour light-dark cycle, is present in almost all cells in the body. The clock regulates fundamental biological processes, and circadian disruption is associated with the onset and progression of various diseases including diabetes and cancer. Circadian medicine aims to target the circadian clock and optimally time treatment administrations. However, it remains challenging to determine the circadian time of the patient or the tissue of interest. Here, we developed tauFisher, a computational pipeline that can accurately predict the circadian time for a single sample of transcriptomic data. We highlight tauFisher´s performance on datasets collected from various tissues using different assay methods including microarray, bulk RNA sequencing, and single cell RNA sequencing, demonstrating that tauFisher is an accessible tool for adapting the existing timestamp-less datasets for circadian studies.

The circadian clock is robust in the skin, an organism’s first line of defense against environmental fluctuations and insults. The clock’s proper function is essential for maintaining skin homeostasis and optimizing skin’s response to stressors. Studying the circadian clock in the skin provides insights into disease development and management. We collected time series of single cell RNA sequencing data from mouse skin and discovered different circadian clock properties and differential rhythmic processes in dermal fibroblasts and dermal immune cells. Incorporating tauFisher with bootstrapping, we hypothesize that circadian phase heterogeneity may contribute to the dampened amplitude of the collective core clock in dermal immune cells when compared to dermal fibroblasts. We also found that the clock regulates metabolism and immune responses in the dermal fibroblasts and dermal immune cells respectively. Taken together, our data show that within a single tissue, the circadian clock regulates a highly divergent set of genes in different cell types.