Combining bulk and single-cell RNA-sequencing data to reveal Gene expression pattern of smooth muscle cell in pulmonary arterial hypertension Running title：Smooth Muscle Cell Gene Expression in Pulmonary Arterial Hypertension

Abstract

Purpose The study aims to reveal the gene expression patterns of smooth muscle cells (SMCs) in pulmonary arterial hypertension (PAH) by combining bulk RNA-sequencing and single-cell RNA-sequencing technologies. It seeks to understand the cellular heterogeneity and key gene changes in pathological states, contributing to the complex pathophysiology of PAH. Methods The researchers utilized both bulk RNA-seq and scRNA-seq to analyze lung tissue samples from PAH patients and healthy controls. They aimed to integrate these data to identify differentially expressed genes in SMCs and uncover the regulatory networks at play. Bioinformatics analysis was employed to construct a comprehensive gene expression atlas. Results We performed a detailed analysis of single-cell (GSE210248) and bulk RNA (GSE33463 and GSE113439) data, employing rigorous quality control and PCA to identify gene variability. It discovered 10 cell types through UMAP clustering and analyzed gene differences, particularly focusing on 23 lncRNAs in smooth muscle cells and their roles in key metabolic and immune pathways. Further, it linked thousands of differentially expressed genes with critical lncRNAs like MALAT1 and EPB41L4A-AS1, uncovering their significant roles in PAH and intricate regulatory networks involving various molecular interactions. Conclusions While the specific conclusions were not accessible in the initial sections, the study likely provides insights into the gene expression patterns of SMCs in PAH, offering potential new biomarkers and therapeutic targets. It aims to advance the understanding of PAH's pathogenesis and contribute to better treatment strategies.