Single-cell multi-omics data reveal heterogeneity in liver tissue microenvironment induced by hypertension

Hypertension (HTN) may induce liver damage; however, the effects on liver cell subpopulations remain obscure. Understanding these microenvironmental changes could offer early HTN and liver disease indicators. We employed single-cell multi-omics and histone chromatin immunoprecipitation sequencing (ChIP-seq) to scrutinize microenvironmental alterations between normal and HTN liver tissues. Our analysis revealed an HTN-related hepatocyte subpopulation, termed "Hepatocytes_1," via single-cell RNA sequencing (scRNA-seq). Five potential pathogenic genes (UPB1, SDS, PCCA, CYP3A4, and PPARGC1A) were identified in Hepatocytes_1. Additionally, the regulatory network of cis-regulatory elements (CREs) in genes within Hepatocytes_1 was unveiled using single-cell assay for transposase accessible chromatin (ATAC) sequencing (scATAC-seq) and histone ChIP-seq. Specifically, the active promoter of the disease-associated gene CYP3A4 formed a transcription factor (TF)-mediated regulatory network, resulting in heightened expression in HTN cells. The enhancer-mediated regulatory relationship between NR1H4 and UPB1 serves as a potential regulator in maintaining hepatic metabolic homeostasis in response to HTN-induced disturbances. The identification of HTN-related gene markers and CREs in the liver provides novel insights for HTN prevention and therapeutic targeting.