title: In vivo single-cell detection of metabolic oscillations in stem cells.
abstract: Through the use of bulk measurements in metabolic organs, the circadian clock was shown to play roles in organismal energy homeostasis. However, the relationship between metabolic and circadian oscillations has not been studied in vivo at a single-cell level. Also, it is unknown whether the circadian clock controls metabolism in stem cells. We used a sensitive, noninvasive method to detect metabolic oscillations and circadian phase within epidermal stem cells in live mice at the single-cell level. We observe a higher NADH/NAD+ ratio, reflecting an increased glycolysis/oxidative phosphorylation ratio during the night compared to the day. Furthermore, we demonstrate that single-cell metabolic heterogeneity within the basal cell layer correlates with the circadian clock and that diurnal fluctuations in NADH/NAD+ ratio are Bmal1 dependent. Our data show that, in proliferating stem cells, the circadian clock coordinates activities of oxidative phosphorylation and glycolysis with DNA synthesis, perhaps as a protective mechanism against genotoxicity.
authors.affiliation: Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, University of California, Irvine, Irvine, CA 92037, USA; Laboratory for Optics and Biosciences, École Polytechnique, 91128 Palaiseau Cedex, France.
authors.forename: Chiara
authors.initials: C
authors.lastname: Stringari
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92037, USA; State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92037, USA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Geyfman
authors.affiliation: Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, University of California, Irvine, Irvine, CA 92037, USA.
authors.forename: Viera
authors.initials: V
authors.lastname: Crosignani
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92037, USA; Department of Medicine, School of Medicine, University of California, Irvine, Irvine, CA 92037, USA; Center for Complex Biological System, University of California, Irvine, Irvine, CA 92037, USA; Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, CA 92037, USA. Electronic address: bogi@uci.edu.
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, University of California, Irvine, Irvine, CA 92037, USA; Center for Complex Biological System, University of California, Irvine, Irvine, CA 92037, USA. Electronic address: egratton@uci.edu.
authors.forename: Enrico
authors.initials: E
authors.lastname: Gratton
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D057906:Circadian Clocks / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D006019:Glycolysis; D006706:Homeostasis; D006801:Humans; D051379:Mice; D010085:Oxidative Phosphorylation; D056950:Period Circadian Proteins / Q000235:genetics; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D056950:Period Circadian Proteins