Oit3, a promising hallmark gene for targeting liver sinusoidal endothelial cells

Area of Science:

• Hepatology
• Vascular Biology
• Genetics

Background:

• Liver sinusoidal endothelial cells (LSECs) are crucial for liver homeostasis and disease pathology.
• Lack of specific LSEC hallmark genes and Cre mouse lines hinders research into liver vascular disorders.

Purpose of the Study:

• To identify a specific hallmark gene for LSECs.
• To develop a novel LSEC-specific Cre mouse model for disease research.

Main Methods:

• Comparative gene expression analysis of liver endothelial cells (ECs).
• Single-cell RNA sequencing (scRNA-seq) and database analysis.
• Construction and validation of inducible Oit3-CreERT2 transgenic mice crossed with ROSA26-tdTomato reporter mice.

Main Results:

• Oit3 was identified as a predominant marker in midlobular liver ECs.
• Oit3-CreERT2-tdTomato mice showed specific tdTomato expression in LSECs within the liver.
• Isolated tdTomato+ cells confirmed LSEC identity with distinct fenestrae and EC marker expression.

Conclusions:

• Oit3 is a reliable hallmark gene for LSEC identification and tracing.
• The developed Oit3-CreERT2-tdTomato mouse model offers a powerful platform for investigating LSEC functions in liver diseases.