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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
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Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
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Updated: Nov 13, 2025

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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The circadian oscillator analysed at the single-transcript level.

Nicholas E Phillips1, Alice Hugues1,2, Jake Yeung1

  • 1Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Molecular Systems Biology
|March 15, 2021
PubMed
Summary
This summary is machine-generated.

Single-cell analysis reveals circadian clock gene mRNA levels vary greatly between cells. Circadian phase appears to be regulated post-transcriptionally, not solely by mRNA counts.

Keywords:
circadian oscillatorsingle cellssmFISHstochastic gene expressiontranscriptional bursting

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Area of Science:

  • Cellular and Molecular Biology
  • Chronobiology
  • Systems Biology

Background:

  • The circadian clock regulates daily rhythms through gene expression.
  • Population-level studies show rhythmic expression of core clock genes.
  • Single-cell mRNA dynamics of these genes remain largely uncharacterized.

Purpose of the Study:

  • To investigate single-cell mRNA dynamics of core circadian clock genes (Rev-erbα, Cry1, Bmal1).
  • To model and quantify sources of mRNA variability in single cells over 24 hours.
  • To determine how circadian phase is encoded at the single-cell level.

Main Methods:

  • Single-molecule fluorescence in situ hybridization (smFISH) to measure mRNA counts.
  • Time-course experiments in mouse fibroblasts.
  • Development of a probabilistic model for multivariate mRNA counts (negative binomial mixtures).

Main Results:

  • Mean mRNA levels of Rev-erbα, Cry1, and Bmal1 oscillate over 24 hours.
  • Significant cell-to-cell heterogeneity in mRNA numbers was observed.
  • Circadian time accounted for a small fraction of total mRNA variability; cell size was a notable factor.
  • A probabilistic model successfully integrated transcriptional bursting, circadian time, and cell heterogeneity.

Conclusions:

  • Estimating circadian phase from single-cell mRNA counts presents significant biological challenges.
  • Circadian phase in single cells is likely encoded through post-transcriptional mechanisms.
  • Cell-to-cell variability, including cell size, plays a crucial role in mRNA dynamics.