ArticleMolecular systems biology2021
The circadian oscillator analysed at the single-transcript level.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Transcriptional noise sets fundamental limits to decoding circadian clock phase from single-cell RNA snapshots.iScience · 2026Article
- Time after time - circadian clocks through the lens of oscillator theory.FEBS letters · 2026Review
- Single-Cell Multiomic Analysis of Circadian Rhythmicity in Mouse Liver.bioRxiv : the preprint server for biology · 2025Article
- Exploring cell-to-cell variability and functional insights through differentially variable gene analysis.NPJ systems biology and applications · 2025Article
- Coupling allows robust mammalian redox circadian rhythms despite heterogeneity and noise.Heliyon · 2024Article
- Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.Journal of circadian rhythms · 2024Review
- An improved rhythmicity analysis method using Gaussian Processes detects cell-density dependent circadian oscillations in stem cells.Bioinformatics (Oxford, England) · 2023Article
- An improved rhythmicity analysis method using Gaussian Processes detects cell-density dependent circadian oscillations in stem cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- PRD-2 mediates clock-regulated perinuclear localization of clock gene RNAs within the circadian cycle ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Inference and uncertainty quantification of stochastic gene expression via synthetic models.Journal of the Royal Society, Interface · 2022Article
- An effective model of endogenous clocks and external stimuli determining circadian rhythms.Scientific reports · 2021Article
- The circadian oscillator analysed at the single-transcript level.Molecular systems biology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The circadian clock is an endogenous and self-sustained oscillator that anticipates daily environmental cycles. While rhythmic gene expression of circadian genes is well-described in populations of cells, the single-cell mRNA dynamics of multiple core clock genes remain largely unknown. Here we use single-molecule fluorescence in situ hybridisation (smFISH) at multiple time points to measure pairs of core clock transcripts, Rev-erbα (Nr1d1), Cry1 and Bmal1, in mouse fibroblasts. The mean mRNA level oscillates over 24 h for all three genes, but mRNA numbers show considerable spread between cells. We develop a probabilistic model for multivariate mRNA counts using mixtures of negative binomials, which accounts for transcriptional bursting, circadian time and cell-to-cell heterogeneity, notably in cell size. Decomposing the mRNA variability into distinct noise sources shows that clock time contributes a small fraction of the total variability in mRNA number between cells. Thus, our results highlight the intrinsic biological challenges in estimating circadian phase from single-cell mRNA counts and suggest that circadian phase in single cells is encoded post-transcriptionally.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.