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Updated: May 14, 2026
Isolation and Characterization of Mouse Primary Liver Sinusoidal Endothelial Cells
Published on: December 16, 2021
Nuclear receptor atlas of female mouse liver parenchymal, endothelial, and Kupffer cells
Zhaosha Li1, J Kar Kruijt, Ronald J van der Sluis
1Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands.
Abstract:
The liver consists of different cell types that together synchronize crucial roles in liver homeostasis. Since nuclear receptors constitute an important class of drug targets that are involved in a wide variety of physiological processes, we have composed the hepatic cell type-specific expression profile of nuclear receptors to uncover the pharmacological potential of liver-enriched nuclear receptors. Parenchymal liver cells (hepatocytes) and liver endothelial and Kupffer cells were isolated from virgin female C57BL/6 wild-type mice using collagenase perfusion and counterflow centrifugal elutriation. The hepatic expression pattern of 49 nuclear receptors was generated by real-time quantitative PCR using the NUclear Receptor Signaling Atlas (NURSA) program resources. Thirty-six nuclear receptors were expressed in total liver. FXR-α, EAR2, LXR-α, HNF4-α, and CAR were the most abundantly expressed nuclear receptors in liver parenchymal cells. In contrast, NUR77, COUP-TFII, LXR-α/β, FXR-α, and EAR2 were the most highly expressed nuclear receptors in endothelial and Kupffer cells. Interestingly, members of orphan receptor COUP-TF family showed a distinct expression pattern. EAR2 was highly and exclusively expressed in parenchymal cells, while COUP-TFII was moderately and exclusively expressed in endothelial and Kupffer cells. Of interest, the orphan receptor TR4 showed a similar expression pattern as the established lipid sensor PPAR-γ. In conclusion, our study provides the most complete quantitative assessment of the nuclear receptor distribution in liver reported to date. Our gene expression catalog suggests that orphan nuclear receptors such as COUP-TFII, EAR2, and TR4 may be of significant importance as novel targets for pharmaceutical interventions in liver.
Insights
This study maps nuclear receptor expression in liver cells, identifying key targets like COUP-TFII, EAR2, and TR4 for potential new liver drug development.
Area of Science:
- Hepatology
- Molecular Biology
- Pharmacology
Background:
- Liver homeostasis relies on synchronized functions of diverse cell types.
- Nuclear receptors are crucial drug targets involved in numerous physiological processes.
- Understanding liver cell-specific nuclear receptor expression can reveal pharmacological potential.
Purpose of the Study:
- To generate a comprehensive hepatic cell type-specific expression profile of nuclear receptors.
- To identify liver-enriched nuclear receptors with potential as novel drug targets.
Main Methods:
- Isolation of parenchymal liver cells (hepatocytes) and liver endothelial/Kupffer cells from mice.
- Real-time quantitative PCR analysis of 49 nuclear receptors using NUclear Receptor Signaling Atlas (NURSA) resources.
- Generation of hepatic expression patterns for nuclear receptors.
Main Results:
- Thirty-six nuclear receptors were detected in total liver.
- Hepatocytes showed high expression of FXR-α, EAR2, LXR-α, HNF4-α, and CAR.
- Endothelial and Kupffer cells exhibited high expression of NUR77, COUP-TFII, LXR-α/β, FXR-α, and EAR2.
- Orphan receptors COUP-TFII, EAR2, and TR4 displayed distinct cell-type-specific expression patterns.
Conclusions:
- This study provides the most complete quantitative assessment of nuclear receptor distribution in the liver to date.
- The generated gene expression catalog highlights orphan nuclear receptors (COUP-TFII, EAR2, TR4) as significant potential targets for pharmaceutical interventions in liver diseases.
