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Updated: Dec 22, 2025
10:38
Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
Published on: September 27, 2012
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Noise-driven cellular heterogeneity in circadian periodicity
Yan Li1, Yongli Shan1, Ravi V Desai2,3
1Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111.
Summary
Cellular heterogeneity, or cell-to-cell variability, is linked to aging and disease. This study reveals that nonheritable cellular noise significantly drives variations in circadian rhythms, suggesting circadian period as a marker for cellular noise.
Area of Science:
- Cell Biology
- Chronobiology
- Systems Biology
Background:
- Nongenetic cellular heterogeneity contributes to aging and disease.
- The precise origins of cell-to-cell variability remain unclear.
- Circadian rhythms exhibit phenotypic heterogeneity even in clonal cell populations.
Purpose of the Study:
- Investigate the mechanisms underlying cell-to-cell variability in circadian oscillations.
- Quantify the contributions of heritable and nonheritable factors to circadian period variation.
- Explore the relationship between circadian rhythms and intercellular heterogeneity.
Main Methods:
- Utilized a fully automated tracking and analysis pipeline.
- Examined circadian period length in thousands of single cells and hundreds of clonal cell lines.
- Applied a variance partitioning model to estimate factor contributions.
Main Results:
- Longer circadian period length correlated with increased intercellular heterogeneity.
- Nonheritable noise was identified as the predominant driver of intercellular circadian period variation.
- A noise-enhancing drug administration reversibly increased both circadian period length and variance.
Conclusions:
- Established a link between circadian oscillations and intercellular heterogeneity, driven by nonheritable noise.
- Circadian period can serve as an indicator of cellular noise.
- Circadian period variation may be a target for drug screening and noise control strategies.
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