Cardiomyocytes have mosaic patterns of protein expression

Area of Science:

• Cardiovascular Biology
• Proteomics
• Cellular Heterogeneity

Background:

• Skeletal muscle fibers (fast-twitch and slow-twitch) display distinct gene and protein expression patterns.
• Immunohistochemical staining reveals a mosaic distribution of these proteins within skeletal myocytes.
• It is hypothesized that cardiac myocytes may exhibit similar differential protein expression between mature cardiomyocytes.

Purpose of the Study:

• To investigate potential differential protein expression patterns in mature cardiomyocytes.
• To identify proteins with mosaic expression across cardiomyocytes using the Human Protein Atlas database.
• To correlate protein expression with gene expression and open chromatin data.

Main Methods:

• Utilized the HPASubC tool on over 52,000 cardiac images from the Human Protein Atlas.
• Performed immunohistochemical analysis to identify differential protein expression.
• Matched identified proteins with open chromatin and gene expression data.
• Validated specific proteins (MYL3, MYL4, PAM, MYOM1) for atrial/ventricular expression patterns.

Main Results:

• Identified 143 putative proteins exhibiting mosaic expression patterns across cardiomyocytes.
• Validated four proteins (MYL3, MYL4, PAM, MYOM1) with distinct atrial or ventricular expression.
• Observed histone H3K27 acetylation patterns consistent with atrial/ventricular expression for the validated genes.

Conclusions:

• Cardiac myocytes display a mosaic pattern of protein expression, contrary to the assumption of homogeneity.
• This previously uncharacterized heterogeneity in protein expression may influence individual cardiomyocyte function and disease susceptibility.
• The findings highlight a fundamental biological process impacting cardiomyocyte biology.