A time- and space-resolved nuclear receptor atlas in mouse liver

Area of Science:

• Hepatology and Molecular Biology
• Endocrinology and Metabolism

Background:

• Liver homeostasis relies on a complex transcription factor network, particularly nuclear receptors (NRs).
• NRs integrate extracellular signals (hormones, lipids) to regulate hepatic physiology.
• Knowledge of NR function across diverse liver cell populations remains incomplete.

Purpose of the Study:

• To comprehensively map the expression of nuclear receptors in the mouse liver.
• To investigate NR expression patterns in relation to time, diet, and specific liver cell types.
• To link NR subtissular localization to specialized liver functions.

Main Methods:

• Quantitative analysis of NR expression in whole mouse liver under varying dietary conditions.
• NR isoform profiling in purified liver cell populations (hepatocytes, cholangiocytes, immune cells, stellate cells, sinusoidal cells).
• Integration of single-cell RNA sequencing data to determine NR zonation within the liver.

Main Results:

• Several NRs (e.g., Nr1d1, Nr1d2, Nr1c2, Nr1f3) showed robust cyclical expression, enhanced by time-restricted feeding.
• NR expression varied significantly across different liver cell types, with some isoforms highly cell-specific (e.g., Nr1h4, Nr1b1).
• Single-cell analysis revealed distinct NR zonation patterns in hepatocytes and other liver cells, correlating with functional specialization.

Conclusions:

• This study provides a detailed spatiotemporal atlas of nuclear receptor expression in the mouse liver.
• NR expression is dynamically regulated by feeding patterns and is cell-type specific within the liver.
• The findings establish a link between NR localization and liver functional zonation, advancing our understanding of hepatic regulation.