Related Experiment Video
Updated: Jun 20, 2025
Single Cell Transcriptional Profiling of Adult Mouse Cardiomyocytes
Published on: December 28, 2011
Single-cell RNA-sequencing identifies unique cell-specific gene expression profiles in high-grade cardiac allograft
Insights
Single-cell RNA sequencing of peripheral blood mononuclear cells identified unique gene expression patterns in cardiac allograft vasculopathy (CAV). These findings suggest potential peripheral gene expression biomarkers for diagnosing CAV after heart transplantation.
Area of Science:
- Immunology
- Cardiovascular Science
- Genomics
Background:
- Cardiac allograft vasculopathy (CAV) is a major cause of graft failure and mortality post-heart transplantation (HT).
- Current diagnosis relies on invasive coronary angiography, necessitating less invasive alternatives.
- Identifying peripheral biomarkers for CAV is crucial for early detection and management.
Purpose of the Study:
- To identify cell-specific gene expression profiles in CAV using single-cell RNA sequencing.
- To explore potential peripheral biomarkers for CAV diagnosis.
Main Methods:
- Single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from HT recipients with and without CAV.
- Differential gene expression, cell composition, and T cell receptor repertoire analyses were conducted.
- Weighted gene co-expression network analysis identified enriched pathways.
Main Results:
- Subtle but significant increases in CD4+ T central memory cells and monocytes were observed in high-grade CAV.
- 745 differentially expressed genes were identified in a cell-specific manner in high-grade CAV.
- Enriched pathways included inflammation and angiogenesis; T cell clonality did not differ significantly.
Conclusions:
- Single-cell transcriptomic analysis reveals unique, cell-specific gene expression patterns in CAV.
- Peripheral gene expression patterns hold potential as biomarkers for CAV diagnosis.
- Further research can validate these findings for clinical application.
Background:
Cardiac allograft vasculopathy (CAV), a diffuse thickening of the intima of the coronary arteries and microvasculature, is the leading cause of late graft failure and mortality after heart transplantation (HT). Diagnosis involves invasive coronary angiography, which carries substantial risk, and minimally-invasive approaches to CAV diagnosis are urgently needed. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to identify cell-specific gene expression profiles in CAV.
Methods:
Whole blood was collected from 22 HT recipients with angiographically-confirmed CAV and 18 HT recipients without CAV. PBMCs were isolated and subjected to single-cell RNA-sequencing using a 10X Genomics microfluidic platform. Downstream analyses focused on differential expression of genes, cell compositional changes, and T cell receptor repertoire analyses.
Results:
Across 40 PBMC samples, we isolated 134,984 cells spanning 8 major clusters and 31 subclusters of cell types. Compositional analyses showed subtle, but significant increases in CD4+ T central memory cells, and CD14+ and CD16+ monocytes in high-grade CAV (CAV-2 and CAV-3) as compared to low-grade or absent CAV. After adjusting for age, gender, and prednisone use, 745 genes were differentially expressed in a cell-specific manner in high-grade CAV. Weighted gene co-expression network analyses showed enrichment for putative pathways involved in inflammation and angiogenesis. There were no significant differences in T cell clonality or diversity with increasing CAV severity.
Conclusions:
Unbiased whole transcriptomic analyses at single-cell resolution identify unique, cell-specific gene expression patterns in CAV, suggesting the potential utility of peripheral gene expression biomarkers in diagnosing CAV.
