Related Experiment Video
Updated: Jun 27, 2026
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
Kaushik Amancherla1, Kelly H Schlendorf2, Nelson Chow2
1Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Insights
Single-cell analysis reveals distinct gene expression patterns in cardiac allograft vasculopathy (CAV), offering potential for new diagnostic biomarkers and targeted therapies to improve heart transplant outcomes.
Area of Science:
- Immunology
- Cardiology
- Genomics
Background:
- Cardiac allograft vasculopathy (CAV) is a primary cause of graft failure and mortality post-heart transplantation (HT).
- Current diagnostic and therapeutic strategies for CAV are insufficient.
Purpose of the Study:
- To investigate cell-specific gene expression profiles and T cell receptor repertoires in CAV using single-cell RNA-sequencing.
- To identify novel biomarkers and therapeutic pathways for CAV pathogenesis.
Main Methods:
- Single-cell RNA-sequencing was performed on peripheral blood mononuclear cells (PBMCs) from HT recipients with and without CAV.
- Analyses included differential gene expression, cell composition changes, and T cell receptor repertoire analysis.
Main Results:
- Significant increases in CD4+ T central memory cells and monocytes were observed in high-grade CAV.
- 745 cell-specific differentially expressed genes were identified, enriched in inflammation and angiogenesis pathways.
- 68 potential therapeutic targets were prioritized, including those with existing cardiovascular drugs.
Conclusions:
- Single-cell transcriptomic analysis reveals unique, cell-specific gene expression patterns in CAV.
- Peripheral gene expression biomarkers show potential for CAV diagnosis.
- Targeting identified pathways may offer new therapeutic strategies for CAV.
Background:
Cardiac allograft vasculopathy (CAV) is the leading cause of late graft failure and mortality after heart transplantation (HT). Current strategies for early diagnosis and effective treatment of CAV are lacking. Using single-cell RNA-sequencing in peripheral blood mononuclear cells (PBMCs), we sought to investigate cell-specific gene expression profiles and T cell receptor repertoires in CAV that may inform novel biomarkers and pathways to interrupt CAV pathogenesis.
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 31 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). 745 genes were differentially expressed in a cell-specific manner in high-grade CAV, enriched for putative pathways involved in inflammation and angiogenesis. Intersection with the druggable genome prioritized 68 targets, including targets with approved drugs in cardiovascular disease (e.g., canakinumab). 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. Furthermore, precision targeting of these pathways may offer opportunities to mitigate CAV pathogenesis.
More Related Videos
05:54Preparation of a Non-Cardiomyocyte Cell Suspension for Single-Cell RNA Sequencing from a Post-Myocardial Infarction Adult Mouse Heart
Published on: February 3, 2023
10:03Author Spotlight: Nuclei Isolation from Mouse Cardiac Progenitor Cells for Epigenome and Gene Expression Profiling at Single-Cell Resolution
Published on: May 12, 2023
