Single-Cell RNA Sequencing of Human Corpus Cavernosum Reveals Cellular Heterogeneity Landscapes in Erectile Dysfunction.

To assess the diverse cell populations of human corpus cavernosum in patients with severe erectile dysfunction (ED) at the single-cell level.

Penile tissues collected from three patients were subjected to single-cell RNA sequencing using the BD Rhapsody™ platform. Common bioinformatics tools were used to analyze cellular heterogeneity and gene expression profiles from generated raw data, including the packages Seurat, Monocle, and CellPhoneDB.

Disease-related heterogeneity of cell types was determined in the cavernous tissue such as endothelial cells (ECs), smooth muscle cells, fibroblasts, and immune cells. Reclustering analysis of ECs identified an arteriole ECs subcluster and another one with gene signatures of fibroblasts. The proportion of fibroblasts was higher than the other cell populations and had the most significant cellular heterogeneity, in which a distinct subcluster co-expressed endothelial markers. The transition trajectory of differentiation from smooth muscle cells into fibroblasts was depicted using the pseudotime analysis, suggesting that the expansion of corpus cavernosum is possibly compromised as a result of fibrosis. Cell-cell communications among ECs, smooth muscle cells, fibroblasts, and macrophages were robust, which indicated that inflammation may also have a crucial role in the development of ED.

Our study has demonstrated a comprehensive single-cell atlas of cellular components in human corpus cavernosum of ED, providing in-depth insights into the pathogenesis. Future research is warranted to explore disease-specific alterations for individualized treatment of ED.

Frontiers in endocrinology. 2022 Apr 20*** epublish ***

Dong Fang, Xiao-Hui Tan, Wen-Peng Song, Yang-Yang Gu, Jian-Cheng Pan, Xiao-Qing Yang, Wei-Dong Song, Yi-Ming Yuan, Jing Peng, Zhi-Chao Zhang, Zhong-Cheng Xin, Xue-Song Li, Rui-Li Guan

Department of Urology, Peking University First Hospital, Beijing, China., Institute of Urology, Peking University, Beijing, China., Male Reproductive and Sexual Medicine, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.