Single-cell Transcriptome Atlas of the Human Corpus Cavernosum
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE206528 | GEO | 2022/06/23
REPOSITORIES: GEO
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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.
2022-12-07 | GSE168545 | GEO
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.
2024-02-26 | GSE259299 | GEO
Project description:Single-Cell Transcriptomic Atlas of Penile Corpus Cavernosum Aging
| PRJNA708273 | ENA
Project description:Background: Erectile dysfunction (ED) is a prevalent male sexual disorder, commonly associated with hypertension, though the underlying mechanisms remain poorly understood. Objective: This study aims to explore the role of Fatty acid synthase (Fasn) in hypertension-induced ED and evaluate the therapeutic potential of the Fasn inhibitor C75. Materials and Methods: Erectile function was assessed by determining the intracavernous pressure/ mean arterial pressure (ICP/MAP) ratio, followed by the collection of cavernous tissue for transcriptomic and non-targeted metabolomic analyses. In vitro, a concentration of 10-6 M angiotensin II (Ang II) was applied to rat aortic endothelial cells (RAOECs) to establish a model of hypertension. In vivo, spontaneously hypertensive rats (SHR) were randomly divided into two groups. The SHR+C75 group received intraperitoneal injections of C75 at a dose of 2 mg/kg once a week. After five weeks of treatment, the erectile function of the rats was assessed, and penile tissues were harvested for further analysis. Molecular and protein expression were assessed using Western blotting, qRT-PCR, immunofluorescence staining, and immunohistochemistry. Results: The SHR exhibited ED, indicated by reduced maximum ICP/MAP ratios. Histologically, corpus cavernosum tissue of SHR showed elevated fibrosis and endothelial dysfunction. Additionally, increased expression of the NLRP3 inflammasome, Caspase-1, GSDMD, and the pro-inflammatory cytokines IL-1β and IL-18 was observed. Multi-omics analysis revealed significant enrichment in lipid metabolic pathways, with Fasn identified as a hub gene. In vitro, siFasn and C75 enhanced antioxidant markers Nrf2 and HO-1, reduced ROS accumulation, and suppressed NLRP3 and GSDMD levels. In vivo, C75 treatment restored endothelial function and reversed erectile dysfunction, accompanied by decreased oxidative stress and pyroptosis in the penile corpus cavernosum. Conclusion: These findings suggest that Fasn inhibition may offer a promising therapeutic strategy for hypertension-induced ED by alleviating oxidative stress and suppressing NLRP3 inflammasome-dependent endothelial cell pyroptosis via activation of the Nrf2/HO-1 pathway.
2024-12-24 | GSE285267 | GEO
Project description: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.
| S-EPMC9314400 | biostudies-literature
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.
2024-06-12 | GSE261487 | GEO
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.
2024-06-12 | GSE261085 | GEO
Project description:Purpose: To identify the molecular phenotype of endothelial cells (EC) isolated from the unique vasculature of the corpus cavernosum. Methods: Human EC derived from corpus cavernosum (HCCEC, n=5), coronary artery (HCAEC, n=4) and umbilical vein (HUVEC, n=3) were grown in culture and mRNA transcripts quantified by Affymetrix GeneChip microarrays. Genes differentially expressed across samples were partitioned around medoids to identify genes with highest expression in HCCEC. Several genes were verified by real-time PCR. The role of claudin 11 (CLDN11) in endothelial cell barrier function was examined by in vitro transendothelial electrical resistance assay. Results: Unsupervised hierarchical clustering of samples using all expressed genes yielded discrete groupings of EC lines according to their in vivo source of origin. 190 genes/transcripts were highly expressed only in cavernosal HCCEC. Gene Ontology classification indicated cavernosal enrichment in genes related to cell adhesion, extracellular matrix (ECM), pattern specification and organogenesis. KEGG pathway analysis showed high expression of gene relating to ECM-receptor interaction, focal adhesions, and cytokine-cytokine receptor interaction. Real-time PCR confirmed expression differences in cadherins 2 and 11, CLDN11, desmoplakin and versican. CLDN11, a component of tight junctions not previously described in ECs, was highly expressed only in HCCEC and its knockdown by siRNA significantly reduced transendothelial electrical resistance in HCCEC. Conclusions: HCCECs displayed expression of transcripts encoding matrix and adhesion proteins that regulate structural and functional characteristics of blood vessels. High expression of the tight junction protein CLDN11 is novel in endothelial cells and contributes to barrier function of cultured HCCEC. Experiment Overall Design: Endothelial cells were grown on 2% gelatin type B (Sigma)/15% fetal bovine serum (Gibco) coated tissue culture dishes in Medium 199 (Gibco) supplemented with 20% FBS, EGM-2MV (Clonetics), L-glutamine and 10,000u/ml Penicillin, 10,000u/ml Streptomycin, and 25mg/ml Fungizone. All cells were grown in a humidified incubator at 37 oC and 5% CO2 with media changed every 2-3 days. Total RNA isolation for the arrays was performed using Qiagen RNeasy mini columns according to manufacturers instructions (RNeasy Mini Handbook). Briefly, cells grown in T-75 culture flasks were trypsinized with 0.25% trypsin/1 mM EDTA (Gibco) between the third and seventh passages and centrifuged to pellet the cells. Next, cells were disrupted and homogenized in RNeasy lysis buffer using a 1ml syringe with 21-gauge needle. Ethanol was added to allow binding of RNA to the silica-gel-based membrane of the mini column. Several washes as well as on-column DNase treatment were used to ensure that contaminants and DNA were effectively removed from the column. Finally, RNA was eluted in approximately 30ul of RNase free water. Experiment Overall Design: Biotin labeled target cRNA was prepared according to the Affymetrix eukaryotic target labeling protocol starting with 5ug total RNA for each sample. Each target was hybridized to an Affymetrix Human U133A GeneChip. GeneChips were washed and scanned at the University of Washingtonâs Center for Expression Arrays according to procedures developed by the manufacturer.
2009-10-03 | E-GEOD-10804 | biostudies-arrayexpress
Project description:Formation of cortical connections requires the precise coordination of several discrete stages. This is particularly significant with regard to the corpus callosum, the largest white matter structure bridging both cerebral hemispheres, whose development undergoes several dynamic stages including the crossing of axon projections, the elimination of exuberant projections, and the myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic expression profiles were then segregated into five separate protein clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure.
2017-03-29 | PXD005271 | Pride
Project description:(Erectile dysfunction) ED during the radical prostatectomy (RP) treatment is caused by surgical injury of the cavernous nerve which is the final neuronal pathways of penile erection. We performed microarray experiment focused on theto understanding the gene signature alteration in the corporal cavernous tissue of the CNI-induced ED rat model.
2012-12-31 | GSE31247 | GEO