Single-cell transcriptome atlas of the human corpus cavernosum

Abstract

The corpus cavernosum is the most important structure for penile erection, and its dysfunction causes many physiological and psychological problems. However, its cellular heterogeneity and signalling networks at the molecular level are poorly understood because of limited access to samples. Here, we profile 64,993 human cavernosal single-cell transcriptomes from three males with normal erection and five organic erectile dysfunction patients. Cell communication analysis reveals that cavernosal fibroblasts are central to the paracrine signalling network and regulate microenvironmental homeostasis. Combining with immunohistochemical staining, we reveal the cellular heterogeneity and describe a detailed spatial distribution map for each fibroblast, smooth muscle and endothelial subcluster in the corpus cavernosum. Furthermore, comparative analysis and related functional experiments identify candidate regulatory signalling pathways in the pathological process. Our study provides an insight into the human corpus cavernosum microenvironment and a reference for potential erectile dysfunction therapies.

Low-Intensity Pulsed Ultrasound Counteracts Advanced Glycation End Products-Induced Corpus Cavernosal Endothelial Cell Dysfunction via Activating Mitophagy

“…Furthermore, in the diabetic state, apoptosis of ECs is increased, while the expression of cell connexins such as GJA1, CLDN5, and ZO-1 is decreased, leading to vascular leakage and failure to maintain erections [ 34 ]. In addition to impairing endothelial function, long-term diabetes can also cause extensive organic changes in the CC tissue, mainly manifested by morphological changes, decreased numbers of ECs, and increased levels of collagen [ 9 ].…”

“…Bioinformatic analysis based on proteomics studies carried out on human umbilical vascular endothelial cells (HUVECs) revealed that the differentially regulated proteins were involved in various processes such as apoptosis and oxidative stress [ 37 ]. However, as our previous studies have shown that CCECs are more susceptible to diabetic damage than the vascular endothelium [ 9 ], studies based on HUVECs may not accurately reflect the diabetic conditions of CCECs and the cause of DMED. Therefore, we comprehensively evaluated the effects of AGES treatment on CCECs using RNA-seq and identified several highly enriched terms related to mitochondria.…”

“…Furthermore, AGEs damage vascular structure via promoting apoptosis, calcification, senescence, and hyperpermeability in endothelial cells (ECs) [ 7 , 8 ]. Erectile dysfunction (ED) is known as a predictor of cardiovascular disease events, and we have shown that corpus cavernosum endothelial cells (CCECs) are more susceptible to injury than the ECs of other blood vessels [ 9 , 10 ]. However, common and unique factors relating to the damage of CCECs and other types of ECs in diabetes remain unclear.…”

MHA, an interactive website for scRNA-seq data of male genitourinary development and disease

“…We provide simple and detailed clustering classifications. This dataset comes from our previous published study[11]. Human_Prostate_Cancer_Atlas: this dataset contains 16 human prostate samples from three young male organ donors aged 18–31 years [12] and 13 prostate cancer samples from patients aged 61–81 years (12 primary and 1 lymph node metastasis) [13].…”

“…We provide simple and detailed clustering classifications. This dataset comes from our previous published study[11].…”