Cross-species scRNA-seq finds ideal mouse models for aortic dissection mechanisms

Area of Science:

• Cardiovascular Biology
• Translational Medicine
• Genomics

Background:

• Aortic dissection is a severe cardiovascular condition.
• Understanding its cellular mechanisms is crucial for developing effective treatments.
• Mouse models are essential tools for studying aortic dissection pathophysiology.

Purpose of the Study:

• To systematically evaluate the fidelity of five common mouse models for studying aortic dissection.
• To compare the cellular and transcriptional profiles of these models against human aortic dissection data.
• To identify which mouse models best recapitulate specific aspects of human disease pathology.

Main Methods:

• Cross-species single-cell RNA sequencing was employed.
• Data from human aortic dissection was integrated with data from five mouse models (BAPN, Ang-II, Ang-II apoE-/- , elastase, and CaCl2).
• Comparative analysis focused on four key cell types.

Main Results:

• Model-specific transcriptional parallels to human aortic dissection were identified.
• The BAPN model showed similarities in macrophage and fibroblast states.
• The Ang-II apoE-/- model mimicked pathogenic vascular smooth muscle cell phenotypes.
• Endothelial cell dysfunction was a conserved feature across all tested mouse models.

Conclusions:

• The study provides a single-cell-based framework for evaluating mouse models of aortic dissection.
• Specific mouse models exhibit distinct transcriptional similarities to human disease, offering valuable insights.
• This comparative analysis aids in selecting appropriate models for future aortic dissection research.