Spatial transcriptome sequencing of the human corpus cavernosum with normal erectile function

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level and the evolutionary differences among species remain unexplored. In this study, we integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively charted the spatial cellular landscape of human and rat CC under normal and disease conditions. We partitioned CC on the basis of special structures such as cavernous arteries, septum pectiniforme, and tunica albuginea, and described the spatial heterogeneity of cell composition and signaling networks in different regions. Additionally, we observed differences in the proportion of cell subtypes and marker genes among endothelial cells (EC), smooth muscle cells (SMC), and fibroblasts (FB) between humans and rats. Although many signalings involved in the basic biological processes such as translation are relatively conserved between human and rat, they show significant species differences in the pathways such as inflammatory response. Based on the analysis of FB niche, we also found that mechanical force signaling have significant spatial heterogeneity within CC and correlated with the spatial distribution of different FB subtypes. In vitro, soft and hard extracellular matrix (ECM) induced the differentiation of FB into APO+FB or COMP+FB subtype, respectively, and reprogrammed their lipid metabolism. In summary, our study provided a cross-species and physio-pathology transcriptomic atlas of the CC at the single-cell level with high spatial resolution, contributing to further understanding of the molecular anatomy and regulation of penile erection. Spatial transcriptome of human CC tissue with normal function, we cropped part of the tissue cross-sections and tried to include as more as different characteristic regions, such as cavernous arteries, septum pectiniforme, tunica albuginea and most part of cavernosal trabecular.