Abstract P3079: Integrating Existing Cardiac Single-cell RNA Sequencing Datasets To Uncover The Role Of B-cells In Heart Disease

Abstract

Introduction: The role of B-cells in human heart failure remains unclear. To address this knowledge gap, we analyzed publicly available datasets of scRNAseq and snRNAseq from patients with various forms of cardiomyopathy. Methods and Results: We used two public datasets including single cells or single nuclei RNAseq data collected from the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), idiopathic cardiac diseases (ICD), or healthy controls. The first dataset comprised 30 healthy controls and 22 non-ischemic DCM; the second contained 18 controls and 61 with DCM, ARVC, or ICD. Data were normalized and scaled, a UMAP plot was generated, and cells were classified using ScType. B-cells were merged into a single matrix, and the final dataset contained 1100 cells from 32 healthy controls, 59 DCM, and 8 ARVC patients. Four different B-cell clusters were identified. The top 100 biomarkers from each cluster were used to identify B-cell subtypes. Cluster 1 was identified as transitional splenic B-cells; Cluster 2 as plasma cells; Cluster 3 as follicular splenic B-cells; Cluster 4, present only in DCM, as immature B cells. Ingenuity Pathway Analysis (IPA) of the genes enriched in each cluster highlighted that different B cell clusters displayed distinct biological activity, ranging from phagosome formation to B cell receptor signaling and cytokine production. Differentially expressed gene analysis comparing healthy controls to DCM and ARVC showed both similar and disease-specific gene expression patterns in the various B cell clusters. For instance, cluster 2 showed upregulation of oxidative phosphorylation in both DCM and ARVC. On the other hand, DCM cluster 2 showed downregulation of CD40 signaling, while in ARVC the same cluster showed downregulation of IL-6 signaling (Z score >2, p<0.05). Discussion: Our findings suggest that human heart failure is associated with perturbations in B cell gene expression, with both shared and disease-specific features. This data supports the notion that B cells likely play a role in human cardiomyopathy. Further, this data suggests that B-cells play distinct roles in disparate forms of cardiac disease.