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Circadian Rhythms and Gene Regulation

Circadian Rhythms and Gene Regulation

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...

Circadian Rhythms and Gene Regulation

Circadian Rhythms and Gene Regulation

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Transmission Electron Microscopy as the Visualization Technique for Analysis of Circadian Synaptic Plasticity in the Mouse Barrel Cortex

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Single-cell Transcriptomic Variance Analysis Reveals Intercellular Circadian Desynchrony in the Alzheimer's Affected

Henry C Hollis, Anthony Veltri, Ksenija Korac

Biorxiv : the Preprint Server for Biology

|April 3, 2026

Summary

New method ORPHEUS quantifies cellular desynchrony in circadian rhythms. It reveals reduced neuronal synchrony in Alzheimer's Disease (AD) and links higher synchrony to MTORC activity in liver and brain tissues.

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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

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Published on: September 28, 2017

Area of Science:

Chronobiology
Systems Biology
Computational Biology

Background:

Tissue-level biological rhythms emerge from coordinated cellular oscillations.
Distinguishing between changes in cellular oscillator amplitude and temporal coherence is crucial for understanding rhythm regulation.

Purpose of the Study:

To develop and validate a novel analytical method, ORPHEUS (Oscillatory Rhythm Phase Heterogeneity Estimated Using Statistical-moments), for quantifying cellular desynchrony.
To apply ORPHEUS to investigate intercellular synchrony in mouse and human tissues and its relation to disease and biological pathways.

Main Methods:

ORPHEUS leverages the unique 12-hour rhythmic signature in intercellular expression variance to quantify cellular desynchrony.
The method was validated using in silico models and experimental data from the mouse suprachiasmatic nucleus (SCN).
ORPHEUS was applied to time-course single-cell data from mouse liver and human brain.

Main Results:

Circadian synchrony was found to be higher in cells and samples with elevated MTORC activity in both mouse liver and human brain.
A significant loss of cellular synchrony was observed in excitatory neurons from individuals with Alzheimer's Disease (AD) dementia.
ORPHEUS successfully decoupled the influences of cellular amplitude and synchrony.

Conclusions:

ORPHEUS provides a novel and interpretable tool for analyzing circadian coordination in time-course single-cell data.
Disruptions in cellular synchrony, particularly in neuronal populations, may be a key feature of Alzheimer's Disease.
MTORC activity is positively associated with circadian synchrony across different tissues.