Year: 2023
Type: article
Abstract: The circadian clock modulates most of human physiology. However, the organization of tissue-specific gene expression rhythms is still poorly known, as well as age and sex dependencies. We leveraged the Genotype-Tissue Expression project (GTEx) using a novel algorithm to assign a unique circadian phase to 914 individuals and transfer time information from stronger to weaker clocks. These donor internal phases allowed us to identify and compare programs of rhythmic gene expression in 46 tissues. Clock transcripts showed highly conserved phase and amplitude relationships across tissues, and were tightly synchronized across the body. Tissue rhythmic gene expression programs differed in breadth, covering global and tissue-specific functions, including metabolic pathways and systemic responses such as heat shock. The circadian clock structure and amplitude was indistinguishable across sexes and age groups. However, overall gene expression rhythms were highly sex-dimorphic and more sustained in females. Moreover, rhythmic programs dampened with age across the body. Together, our stratified analysis unveiled a rich organization of sex- and age-specific circadian gene expression rhythms in humans. One sentence summary Circadian phase inference of 914 GTEx donors reveals sex- and age-dependent rhythmic gene expression programs across 46 human tissues.
Source: Science
Authors: Lorenzo Talamanca, Cédric Gobet, Felix Naef
Institution: École Polytechnique Fédérale de Lausanne
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund
OpenAlex ID: W4318960495