ArticlePLoS genetics2014
Cell type-specific functions of period genes revealed by novel adipocyte and hepatocyte circadian clock models.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 117 citations in OpenAlex.
- Restoration of circadian rhythm as novel targets against sarcopenia.Chinese medical journal · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- PER3 expression in granulosa cells of women with polycystic ovary syndrome: a potential role of the ovarian peripheral clock in infertility.Molecular biology reports · 2026Article
- Steroid hormone receptors through Cry2 are key players in the circadian clock response to serum.Nature communications · 2025Article
- Salivary Circadian Gene Expression as a Molecular Indicator of Early Cognitive Impairment in Shift Workers: A Cross-Sectional Study of 300 Adults.Journal of molecular neuroscience : MN · 2025Article
- Circadian rhythms of macrophages are altered by the acidic tumor microenvironment.EMBO reports · 2024Article
- Functional and regulatory diversification of Period genes responsible for circadian rhythm in vertebrates.G3 (Bethesda, Md.) · 2024Article
- Hypermetabolic state is associated with circadian rhythm disruption in mouse and human cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coordination of rhythmic RNA synthesis and degradation orchestrates 24- and 12-h RNA expression patterns in mouse fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Coordination of rhythmic RNA synthesis and degradation orchestrates 24-hour and 12-hour RNA expression patterns in mouse fibroblasts.bioRxiv : the preprint server for biology · 2023Article
- An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells.NPJ systems biology and applications · 2023Article
- Nutritional compensation of the circadian clock is a conserved process influenced by gene expression regulation and mRNA stability.PLoS biology · 2023Article
- The circadian rhythm: an influential soundtrack in the diabetes story.Frontiers in endocrinology · 2023Review
- In vitro characterisation of murine pre-adipose nucleated cells reveals electrophysiological cycles associated with biological clocks.Electrophoresis · 2022Article
- Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma.Journal of Cancer · 2022Article
- Circadian Clock Genes Are Correlated with Prognosis and Immune Cell Infiltration in Colon Adenocarcinoma.Computational and mathematical methods in medicine · 2022Article
- NF-κB modifies the mammalian circadian clock through interaction with the core clock protein BMAL1.PLoS genetics · 2021Article
- Modulation of circadian clock by crude drug extracts used in Japanese Kampo medicine.Scientific reports · 2021Article
- Natural antisense transcript ofGenes & development · 2021Article
- Targeted modification of the Per2 clock gene alters circadian function in mPer2luciferase (mPer2Luc) mice.PLoS computational biology · 2021Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
In animals, circadian rhythms in physiology and behavior result from coherent rhythmic interactions between clocks in the brain and those throughout the body. Despite the many tissue specific clocks, most understanding of the molecular core clock mechanism comes from studies of the suprachiasmatic nuclei (SCN) of the hypothalamus and a few other cell types. Here we report establishment and genetic characterization of three cell-autonomous mouse clock models: 3T3 fibroblasts, 3T3-L1 adipocytes, and MMH-D3 hepatocytes. Each model is genetically tractable and has an integrated luciferase reporter that allows for longitudinal luminescence recording of rhythmic clock gene expression using an inexpensive off-the-shelf microplate reader. To test these cellular models, we generated a library of short hairpin RNAs (shRNAs) against a panel of known clock genes and evaluated their impact on circadian rhythms. Knockdown of Bmal1, Clock, Cry1, and Cry2 each resulted in similar phenotypes in all three models, consistent with previous studies. However, we observed cell type-specific knockdown phenotypes for the Period and Rev-Erb families of clock genes. In particular, Per1 and Per2, which have strong behavioral effects in knockout mice, appear to play different roles in regulating period length and amplitude in these peripheral systems. Per3, which has relatively modest behavioral effects in knockout mice, substantially affects period length in the three cellular models and in dissociated SCN neurons. In summary, this study establishes new cell-autonomous clock models that are of particular relevance to metabolism and suitable for screening for clock modifiers, and reveals previously under-appreciated cell type-specific functions of clock genes.
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