Single-Cell Transcriptomic Reveals the Involvement of Cell-Cell Junctions in the Early Development of Hypertrophic...

Area of Science:

• Cardiovascular Biology
• Molecular Biology
• Genetics

Background:

• Endothelial cell-cell junctions are crucial for microvascular integrity.
• Alterations in these junctions are implicated in cardiovascular diseases like hypertrophic cardiomyopathy (HCM).
• The role of endothelial cell-cell junctions and their potential as early biomarkers in HCM progression is not well understood.

Purpose of the Study:

• To investigate changes in endothelial cell-cell junctions during HCM progression.
• To identify potential early diagnostic biomarkers for HCM.
• To explore the underlying mechanisms of endothelial cell-cell junction alterations in HCM.

Main Methods:

• Analysis of single-nucleus RNA-sequencing data from human and mouse hearts.
• Pseudo-timing analysis to predict the onset of junctional abnormalities.
• Cell communication and transcription factor analysis.
• Development and validation of a gene-based prediction model for early HCM detection.

Main Results:

• Significant alterations in tight, gap, and adherens junctions were observed in HCM endothelial cells, particularly capillary ECs.
• Junctional abnormalities were predicted to occur in the early stages of HCM.
• Expression of eight specific cell-cell junction genes showed dynamic changes across HCM progression stages in mice.
• A prediction model based on these eight genes achieved an accuracy of 0.81 in identifying early HCM.

Conclusions:

• Eight cell-cell junction genes are significantly elevated in the early stages of HCM in both human and mouse models.
• These genes represent promising potential biomarkers for the early diagnosis of hypertrophic cardiomyopathy.
• Understanding endothelial cell-cell junction dynamics provides insights into HCM pathogenesis.