Single-Cell Multiomic Analysis of Circadian Rhythmicity in Mouse Liver

Area of Science:

• Chronobiology
• Genomics
• Epigenetics

Background:

• Most organisms exhibit 24-hour circadian rhythms, driven by molecular clocks controlling gene expression.
• These rhythms impact hormonal, metabolic, physiological, and behavioral processes.
• Understanding liver peripheral clocks is crucial for comprehending circadian regulation.

Purpose of the Study:

• To simultaneously characterize gene expression and chromatin accessibility in mouse liver cells across a 24-hour cycle.
• To investigate circadian rhythmicity at single-cell resolution, including cell types and transient states.
• To elucidate the spatiotemporal gene regulatory networks governing liver circadian rhythms.

Main Methods:

• Generation of single-cell RNA and ATAC multiomic data from ~33,000 mouse liver cells.
• Analysis of circadian rhythmicity in gene expression and chromatin accessibility distributions.
• Inference of gene regulatory networks incorporating RNAs, regulatory elements, and transcription factors.

Main Results:

• Circadian rhythmicity detected in distinct liver cell types and transient cell states.
• Characterization of transcriptional bursting and its impact on gene expression distributions.
• Identification of multimodal circadian regulation involving RNAs, DNA elements, and transcription factors.
• Inferred spatiotemporal gene regulatory networks controlling liver circadian physiology.

Conclusions:

• This study provides a comprehensive map of liver circadian transcriptomic and epigenomic landscapes.
• The findings elucidate the function and mechanisms of peripheral liver clocks.
• The approach is applicable to other tissues and species, validated by multiple experimental methods.