Single-Cell Transcriptomic Atlas of Penile Corpus Cavernosum Aging
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ABSTRACT:
PROVIDER: PRJNA708273 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13913449_1.fastq.gz | Fastqsanger.gz | |||
| SRR13913449_2.fastq.gz | Fastqsanger.gz | |||
| SRR13913450_1.fastq.gz | Fastqsanger.gz | |||
| SRR13913450_2.fastq.gz | Fastqsanger.gz | |||
| SRR13913451_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: Molecular mechanisms of penile corpus cavernosum aging and male age-related erectile dysfunction (ED) remain unclear. Here we profiled young and old rat penile corpus cavernousm by single-cell RNA sequencing (scRNA-seq). Methods:To map the single-cell transcriptomic landscape of penile corpus cavernosum during aging, we performed uniform manifold approximation and projection (UMAP), differential gene expression analysis (DGEs), pseudotime analysis and single-cell entropy algorithm to dissect cellular composition and transcriptional heterogeneity. For validation analysis, we further performed immunofluorescence studies on key molecules involved during penile corpus cavernosum aging. Results: After stringent filtering,transcriptomes of 14,879 single cells (8,557 young and 6,322 old) derived from penile corpus cavernosum of 5 young (3 months) and 5 old (23 months) rats were analyzed subsequently. Clustering analysis of cell-type specific gene expression identified 19 cell types, such as smooth muscle cells, endothelial cells, fibroblasts,myofibroblasts and immune cells.Transcriptomic analyses revealed that transcriptional alterations across all cell types exhibited distinct properties rather than universally consistent. DGEs analysis demonstrated that genes related to extracellular matrix organization were highly expressed. Among these cell types, fibroblasts showed apparent heterogeneities. By performing pseudotime and 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). Since eliminating senescent cells or SASP were demonstrated to improve health and life span, we further investigated the distinct senescence-related gene expression signatures across all cell types during aging. Conclusions: We plotted a cellular atlas of penile corpus cavernosum, and revealed the molecular alterations of aging cells, especially fibroblasts. Our work will deepen the understanding of the heterogeneity among certain cell types during penile corpus cavernosum aging and provide novel entry points for the age-associated ED treatment.
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Project description:The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level and the evolutionary differences among species remain unexplored. In this study, we integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively charted the spatial cellular landscape of human and rat CC under normal and disease conditions. We partitioned CC on the basis of special structures such as cavernous arteries, septum pectiniforme, and tunica albuginea, and described the spatial heterogeneity of cell composition and signaling networks in different regions. Additionally, we observed differences in the proportion of cell subtypes and marker genes among endothelial cells (EC), smooth muscle cells (SMC), and fibroblasts (FB) between humans and rats. Although many signalings involved in the basic biological processes such as translation are relatively conserved between human and rat, they show significant species differences in the pathways such as inflammatory response. Based on the analysis of FB niche, we also found that mechanical force signaling have significant spatial heterogeneity within CC and correlated with the spatial distribution of different FB subtypes. In vitro, soft and hard extracellular matrix (ECM) induced the differentiation of FB into APO+FB or COMP+FB subtype, respectively, and reprogrammed their lipid metabolism. In summary, our study provided a cross-species and physio-pathology transcriptomic atlas of the CC at the single-cell level with high spatial resolution, contributing to further understanding of the molecular anatomy and regulation of penile erection.
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