Exploration of neuron heterogeneity in human heart failure with dilated cardiomyopathy through single-cell RNA sequencing analysis

Abstract

Abstract Objective We aimed to explore the heterogeneity of neurons in heart failure with dilated cardiomyopathy (DCM). Methods Single-cell RNA sequencing (scRNA-seq) data of patients with DCM and chronic heart failure and healthy samples from GSE183852 dataset were downloaded from NCBI Gene Expression Omnibus, in which neuron data were extracted for investigation. Cell clustering analysis, differential expression analysis, trajectory analysis, and cell communication analysis were performed, and highly expressed genes in neurons from patients were used to construct a protein-protein interaction (PPI) network and validated by GSE120895 dataset. Results Neurons were divided into six subclusters involved in various biological processes and each subcluster owned its specific cell communication pathways. Neurons were differentiated into two branches along the pseudotime, one of which was differentiated into mature neurons, whereas another tended to be involved in the immune and inflammation response. Genes exhibited branch-specific differential expression patterns. FLNA, ITGA6, ITGA1, and MDK interacted more with other gene-product proteins in the PPI network. The differential expression of FLNA between DCM and control was validated. Conclusion Neurons have significant heterogeneity in heart failure with DCM, and may be involved in the immune and inflammation response to heart failure.

Keywords

• Heart failure
• Dilated cardiomyopathy
• Neuron
• Immune and inflammation response
• Differentiation trajectory