Endothelial cells (ECs) of blood and lymphatic vessels have distinct identity markers that define their specialized functions. Recently, hybrid vasculatures with both blood and lymphatic vessel-specific features have been discovered in multiple tissues. Here, we identify the penile cavernous sinusoidal vessels (pc Ss) as a new hybrid vascular bed expressing key lymphatic EC identity genes Prox1, Vegfr3 and Lyve1. Using single cell transcriptome data of human corpus cavernosum tissue, we found heterogeneity within pc S endothelia and observed distinct transcriptional alterations related to inflammatory processes in hybrid ECs in erectile dysfunction associated with diabetes. Molecular, ultrastructural and functional studies further establish hybrid identity of pc-Ss in mouse, and reveal their morphological adaptations and ability to perform lymphatic-like function in draining high molecular weight tracers. Interestingly, we found that inhibition of the key lymphangiogenic growth factor VEGF-C did not block the development of pc-Ss in mice, distinguishing them from other lymphatic and hybrid vessels analyzed so far. Our findings provide a detailed molecular characterization of hybrid pc-Ss and pave the way for the identification of molecular targets for therapies in conditions of dysregulated penile vasculature, including erectile dysfunction.
Keyphrases
- endothelial cells
- single cell
- lymph node
- growth factor
- gene expression
- rna seq
- cardiovascular disease
- genome wide
- type diabetes
- vascular endothelial growth factor
- prostate cancer
- high throughput
- palliative care
- adipose tissue
- electronic health record
- single molecule
- radical prostatectomy
- heat stress
- weight loss
- data analysis
- heat shock