Region- and Cell-type-Resolved Multiomic Atlas of the Heart

Area of Science:

• Cardiovascular Biology
• Proteomics
• Molecular Cardiology

Background:

• Understanding the heart's molecular network is crucial for deciphering its function and disease mechanisms.
• Previous proteomic studies lacked cell-type and region-specific resolution.
• The molecular basis of dilated cardiomyopathy (DCM) requires further elucidation.

Purpose of the Study:

• To create a comprehensive cell-type and region-resolved proteome atlas of the mouse heart.
• To analyze regional proteomic differences in human hearts, including those with DCM.
• To identify potential therapeutic targets for heart failure.

Main Methods:

• In-depth proteomic analysis of mouse heart cell types and regions.
• Proteomic profiling of human heart tissues from four regions, comparing DCM and unaffected samples.
• Functional experiments to validate therapeutic potential of identified pathways.

Main Results:

• Identified 11,794 proteins across mouse heart cell types and 11,995 across regions.
• Quantified 8201 proteins in human DCM tissue and 8316 in adjacent healthy tissue.
• Found enrichment of the retinoic acid synthesis pathway in DCM ventricles; all-trans retinoic acid rescued heart failure models.

Conclusions:

• The study presents a panoramic heart proteome map, detailing cell-type and regional molecular features.
• Discovered altered transcription factor-target gene axes in DCM.
• Demonstrated the therapeutic efficacy of all-trans retinoic acid for heart failure, offering a valuable resource for cardiovascular research.