Farhan Chaudhry, MS

Wayne State University

“Single-Cell Transcriptional Profiling of Circulating Lymphocytes Associated with Cardiac Fibrosis”
SAEMF/RAMS Medical Student Research Grant

$2,500

Abstract

Previous experiments have utilized single-cell RNA-Sequencing (scRNA-seq) to identify altered gene expression of cells in the heart before myocardial injury and immediately following myocardial injury. scRNA-seq is a novel approach that can individually characterize cells within a population based on their transcriptomic characteristics. Recent studies using scRNA-seq have discovered heterogenous subpopulation of cells that are involved in pathology. It is known that different CD4+ lymphocytic subtypes of peripheral blood mononuclear cells (PBMCs) infiltrate the myocardium following injury and contribute to myocardial interstitial fibrosis. However, genetic and epigenetic changes that alter specific subpopulations of PBMCs leading to fibrosis deposition are unknown. We are interested in utilizing scRNA-seq to identify gene expression changes of CD4+ PBMCs in the peripheral blood in an animal chronic pressure overload model. We hypothesize that circulating CD4+ PBMC subpopulation sizes are altered in association with myocardial fibrotic deposition from chronic pressure overload. For our Aim, we propose to extract blood from aortic-banded rats that exhibit global myocardial fibrosis. The PBMCs from the blood will be analyzed with scRNA-seq and bulk-RNA-seq. CIBERSORT software will deconvolute the bulk-RNA-seq data with the scRNA-seq data to obtain relative PBMC subpopulation sizes. We will attempt to assess whether alterations to PBMC subpopulations is associated with myocardial fibrosis deposition. This proposed study will serve as a pilot study to gather preliminary data on the relative PBMC genetic-subpopulation alterations associated with cardiac fibrosis deposition. The preliminary data obtained from this pilot study will be used to apply for larger grants.

Myocardial interstitial fibrosis is a crucial factor in the worsening of heart failure leading to cardiac decompensation and recurrent hospitalizations. It is known that there is a switch in lymphocytic subpopulations from pro-inflammatory infiltrates to reparative infiltrates leading to myocardial fibrosis. Characterizing these specific subpopulations of lymphocytes and their relative presence in the peripheral blood may lead to improved diagnostic capabilities and targets for fibrosis therapy.

Research Results

Dr. Chaudhry is still completing the project.