Molecular and spatial signatures of human and rat corpus cavernosum physiopathological processes at single-cell resolution

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats. Based on the analysis of the fibroblast (FB) niche, we also find that the enrichment scores of mechanical force signaling vary across different regions and correlate with the spatial distribution of FB subtypes. In vitro, the soft and hard extracellular matrix (ECM) induces the differentiation of FBs into apolipoprotein (APO)+ FBs and cartilage oligomeric matrix protein (COMP)+ FBs, respectively. In summary, our study provides a cross-species and physiopathological transcriptomic atlas of the CC, contributing to a further understanding of the molecular anatomy and regulation of penile erection.