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

Abstract

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

Penile cavernous sinusoids are Prox1-positive hybrid vessels

“…S3 ). Additional cluster markers indicated further molecular heterogeneity within the pc-S-EC population, in line with the previous studies [25,32], including high expression of the water channel aquaporin 1 (AQP1) in the pc-S-EC1 cluster ( Fig. S3 ).…”

“…S1 ). Based on known molecular signatures and in line with previous analysis [25,32], we annotated one cluster of penile cavernous arterial ECs (pc-A-ECs) expressing arterial markers (e.g. HEY1 , GJA5 , VEGFC ), and three clusters of penile cavernous sinusoidal ECs (pc-S-EC1-3) expressing venous markers (e.g.…”

Study on the mechanism of aging-related erectile dysfunction based on bioinformatics and experimental verification

“…Notably, NO produced by endothelial cells has also been shown to have anti-fibrotic effects (31). Further, the single-cell RNA sequencing of the human corpus cavernosum revealed a unique subtype of endothelial cells with the hallmarks of fibroblasts (32). Combined with the epithelial to mesenchymal transition in the kidney and heart (33,34), we hypothesize that endothelial cells may transform into fibroblasts and exacerbate the development of fibrosis.…”

Corpora cavernosa fibroblasts mediate penile erection

“…Fibroblasts, previously regarded as static and homogeneous cells, are emerging as a dynamic and heterogeneous cell population ( 46 ). Although fibroblasts constitute the largest cell population in the human CC ( 5 , 6 ), their physiological functions remain largely unexplored. We demonstrate here that perivascular fibroblasts in the mouse CC regulate norepinephrine availability through SLC6A2.…”

“…Recently, fibroblasts have been recognized in the human CC ( 5 , 6 ), but whether they have a role in blood flow regulation has not been addressed.…”