Heterogeneity of fibroblasts is a hallmark of age-associated erectile dysfunction

Background: The prevalence of age-associated erectile dysfunction (ED) increases pronouncedly with age. However, the cellular composition and transcriptomic changes of aging penile corpus cavernosum remain largely unclear. Methods: Herein, we performed single cell sequencing penile corpus cavernosum from five young with normal erectile response and five old rats with ED. Results: Clustering analysis identified 19 cell types, such as fibroblasts, myofibroblasts and immune cells. We next revealed their transcriptomic alterations and investigated novel subpopulations of major cell types. Among them, fibroblasts possessed the largest cell number and showed apparent heterogeneity. By performing single-cell entropy analysis on fibroblasts, we observed the age-associated decrease of entropy, and aged fibroblasts were found to adopt senescent secretory phenotype, as evidenced by the high expression of genes associated with the senescence-associated secretory phenotype (SASP). Finally, we constructed a comprehensive intercellular communication network and highlighted key mediators of crosstalk between fibroblasts and other cell types. Conclusions: We plotted a cellular atlas of aging cells within penile corpus cavernosum, especially fibroblasts. Our work will deepen the understanding of the heterogeneity among certain cell types within aged penile corpus cavernosum, which will generate positive effects on the future treatment of age-associated ED.