Project description:The purpose of conducting transcriptome research in this project is to explore the level of inflammatory response of the graft at the site of corpus cavernosum defect and the influence of the graft on vascularization and tissue regeneration.
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.
Project description:we profiled the scRNA-seq of 4 DMED and 2 normal rat corpus cavernosum. Corpus cavernosum tissue was collected 4 weeks after successful modeling.
Project description:Single-cell transcriptomes of corpus cavernosum from three males with normal erections and five organic erectile dysfunction (ED) patients.
Project description:Penile erection is mediated by the corpora cavernosa, a trabecular-like vascular bed, which enlarges upon vasodilation, but its regulation is not completely understood. Here, we show that perivascular fibroblasts in the corpora cavernosa support vasodilation by reducing norepinephrine availability. We used scRNAseq to investigate fibroblast heterogeneity in the penis.
Project description:We aim to detect differential gene expression using RNA-seq between normal penile epithelial tissue and PB-Cre+ Smad4L/L ApcL/L penile tumors of mice
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.
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.
Project description:Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested that miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profiles in human penile cancer have not been reported before. In this present study, the miRNA profiles were obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous penile tissues via NGS. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired penile tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various types of cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analysis suggested that the putative target genes of the differentially expressed miRNAs were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch, Hedgehog and TGF-β signaling pathways, which were all well-established to be involved in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifing the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights into future investigations aimed to explore the in-depth mechanisms of miRNAs and other small RNAs including piRNAs in penile carcinogenesis regulation and effective target-specific theragnosis.