Single-cell RNA sequencing of neurogenic bladder resulting from pelvic nerve injury in rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE305964 | GEO | 2025/12/23
REPOSITORIES: GEO
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Project description:Pelvic surgeries frequently injure the major pelvic ganglia (MPG), resulting in refractory erectile dysfunction (ED) with limited therapeutic options. Regenerative medicine offers promising avenues for nerve injury-induced ED. Sacral neural crest (NC) cells, the embryonic progenitors of MPG neurons and glia, represent an ideal cell source for targeted neural repair. Here, we establish a robust protocol to differentiate human pluripotent stem cells (hPSCs) into sacral NC cells. Upon transplantation into rats with MPG injury, these cells engraft at the lesion site, differentiate into functional autonomic neurons and glia, and secrete neurotrophic factors. Sacral NC cell therapy reconstructs MPG architecture, promotes axonal regeneration and remyelination, and restores nitrergic innervation. Furthermore, transplantation significantly improves erectile function, evidenced by an increased intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, accompanied by reduced apoptosis and fibrosis and restored smooth muscle and endothelial integrity in the penis. These findings demonstrate that hPSC-derived sacral NC cells offer a novel therapeutic strategy for neurogenic ED by restoring pelvic autonomic nerve structure and function through both neurogenic differentiation and sustained neurotrophic support.
2025-09-24 | GSE299758 | GEO
Project description:Background: Neurogenic bladder (NB) after suprasacral spinal cord injury (SSCI) is an interstitial disease with structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs), which have extensive post-transcriptional regulatory functions, widely participate in the pathogenesis of fibrotic diseases and may be promising new biomarkers and potential therapeutic targets. However, the expression profiles and possible roles of circRNAs in bladder fibrosis and NB after SSCI still remain elusive. Methods: Spinal cord transection at the T10–T11 level was used to construct the NB after SSCI model in rats. The bladders were collected in rats without (sham) and with (SSCI 1-3 groups) NB status. Morphological observation was performed to detect the severity of bladder fibrosis. The expression profiles of mRNAs and circRNAs were detected by transcriptome high-through-put sequencing. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different time periods of SSCI were further analyzed. Moreover, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to investigate the potential functions. In addition, the co-expression network (circRNA–miRNA–mRNA) was constructed to understand the internal regulating relationships of these DEMs and DECs. The top ten common expressed DECs in each NB stage were subjected to Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to verify their expression. Results: Bladder weight, smooth muscle cells hypertrophy, and extracellular matrix gradually increased over time after SSCI. Compared with the normal control (NC) group, 3255 DEMs and 1339 DECs, 3449 DEMs and 1324 DECs, 884 DEMs and 1151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA5775, circRNA3111, and circRNA0586 were significant DECs common to SSCI 1–3 compared with NC group. Moreover, GO enrichment suggested that “inflammatory response”, “inflammatory response” and “chronic inflammatory response” were the key events in NB progression. The KEGG pathway related to “Chemokine signaling pathway”, “IL-17 signaling pathway”, and “TGF-beta signaling pathway” were enriched, implying potential roles in regulatory process. Conclusion: This study provides a systematic perspective on the potential functions of these DEMs and DECs during bladder fibrosis process and NB after SSCI, and could help pave the way for effective therapeutics for this devastating and complex disease.
2023-08-18 | GSE227447 | GEO
Project description:Bilateral freezing of the pelvic ganglia in female rats were performed to denervate the urinary bladder. Sham operated rats were used as controls. The rats were sacrificed 10 days after surgery. The urinary bladders (including the urothelium) were frozen and used for RNA extraction.
2018-03-10 | GSE104539 | GEO
Project description:Bilateral freezing of the pelvic ganglia in female rats were performed to denervate the urinary bladder. Sham operated rats were used as controls. The rats were sacrificed 10 days after surgery. The urinary bladders (including the urothelium) were frozen and used for RNA extraction.
2018-03-10 | GSE104538 | GEO
Project description:Brain-derived extracellular vesicles participate in inter-organ communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome related proteins encapsulated in brain-derived extracellular vesicles are capable of crossing the blood-brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification that combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon identified the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlighted the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offered a potential strategy for the prevention of neurogenic heterotopic ossification after traumatic brain injury.
2023-11-02 | PXD046626 |
Project description:Introduction and Hypothesis: Identify processes contributing to pelvic organ prolapse (POP) by transcriptional profiling of pelvic connective tissue in conjunction with light microscopy. Methods: We performed a frequency matched case-control study of women undergoing hysterectomy. Total RNA, extracted from uterosacral and round ligament samples used to generate labeled cRNA, was hybridized to microarrays and analyzed for the expression of 32,878 genes. Significance Analysis of Microarrays, (Stanford University, CA), identified differentially expressed genes used for ontoanalysis, and quantitative PCR (qPCR) confirmed results. Light microscopy confirmed tissue type and assessed inflammatory infiltration. Results: The analysis of thirty-four arrays revealed 249 differentially expressed genes with fold changes larger than 1.5 fold and false discovery rates M-bM-^IM-$5.2%. Immunity and Defense was the most significant biological process differentially expressed in POP. Selected qPCR confirmed 4 genes. Light microscopy showed no inflammatory infiltrates. Conclusions: Genes enriched for Immunity and Defense contribute to POP independent of inflammatory infiltrates. Keywords: whole tissue (endopelvic fascia) type comparison This was a group matched case control study of 8 women with pelvic organ prolapse versus 9 non-prolapse controls, both undergoing hysterectomy for benign conditions. Two separate pelvic support tissues were collected from each patient. The uterosacral ligament and round ligament tissue was removed at the time of hysterectomy, RNA was extracted and ABI whole genome chips used to identify differences in expression profiles of individual samples. Various ethnic groups, age groups and menopausal status were included.
2008-09-19 | E-GEOD-12852 | biostudies-arrayexpress
Project description:<p>The overall purpose of this University of Utah Pelvic Organ Prolapse Disorder Study was to identify and localize predisposition genes contributing to pelvic organ prolapse (POP). POP cases recruited for this study were identified by one of three methods: high-risk POP pedigree cases, POP sister pairs, and surgically-treated POP cases reporting a family history of POP. <b>High-risk POP pedigree cases</b> were identified using the Utah Population Database (UPDB), a genealogy database of residents in Utah that has been linked to diagnostic ICD9 and CPT codes in medical records at the University of Utah and Intermountain Healthcare. We identified families with a significant excess number of POP cases compared to matched population rates and targeted these individuals for recruitment as well as any other POP cases in the family. <b>POP sister pair cases</b> were identified at the University of Utah Urogyncology clinic for women who had undergone POP surgery and also self-reported one or more sisters who were also surgically treated for POP. POP affection status of all sisters was confirmed either by physical examination or by chart review. <b>Surgically treated-POP cases reporting a family history of POP</b> were identified at the University of Utah Urogyncology clinic by self-report of a family history of POP. Efforts were made to recruit other affected family members and confirm affection status. To obtain DNA, subjects provided either a blood specimen or saliva. Medical records were reviewed by a urogynecologist and diagnostic information for pelvic organ prolapse and stress and overactive bladder were obtained. Collected DNA was genotyped and analyzed. To maintain confidentiality of the familial data, genetic data from only one subject per family has been submitted to dbGaP.</p> <p>Use of the University of Utah Pelvic Organ Prolapse Disorder Study data is limited to investigators studying pelvic floor disorders. These pelvic floor disorders include pelvic organ prolapse, urinary and anal incontinence, and other conditions related to weakening or injury to the muscles and connective tissue in the pelvis as a result of pelvic surgery, pregnancy, or vaginal delivery of a child. These data will be used only for research purposes related to pelvic floor disorders. They will not be used to determine the individual identity of any person or their relationship to another person or for research on non-disease traits.</p>
| phs001439 | dbGaP
Project description:With advancing age, senescent cells accumulate as they are not efficiently cleared by the immune system anymore. Via a senescence-associated secretory phenotype, chronic senescent cells alter the microenvironment, creating an unfavorable milieu for neurogenesis and neurorepair. Using an innovative and rapid aging model, the African turquoise killifish, we have previously demonstrated a dramatic decline in neurogenic potential of non-glial progenitors with age. Even after traumatic brain injury, progenitor proliferation and neuron production was very low in aged killifish in comparison to young adult killifish, and overall neurorepair was incomplete. In the present study, we validated if the senolytic cocktail dasatinib and quercetin (D+Q) could reboot the neurogenic output by clearing chronic senescent cells from the aged killifish brain to re-create the necessary supportive environment. Our results confirm that the aged killifish telencephalon holds a very high senescent cell burden, which we could diminish by short-term systemic D+Q treatment. As a consequence of D+Q administration, proliferation of non-glial progenitors increased and more new neurons were generated and migrated into the parenchyma after injury. Injury-induced inflammation and glial scarring, a phenomenon only seen in aged killifish, remained unaltered. Senolytic treatment with D+Q might thus hold promise for improving brain function in aged populations, and is especially interesting for reviving the neurogenic potential of an already aged central nervous system.
2023-07-20 | PXD036437 | Pride
Project description:Purpose: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study was to identify differentially expressed proteins in the uterosacral ligaments of women with and without pelvic organ prolapse and analyze their relationships to cellular mechanisms involved in the pathogenesis of pelvic organ prolapse. Experimental Design: Uterosacral ligament connective tissue from four patients with pelvic organ prolapse and four control women underwent iTRAQ analysis followed by Ingenuity Pathway Analysis of differentially expressed proteins. Differentially expressed proteins were valideated using western blot analysis. Results: A total of 1789 unique protein sequences were identified in the uterosacral ligament connective tissues. 88 proteins had expression levels that were significantly different between prolapse and control groups (≥1.2-fold). Ingenuity pathway analysis demonstrated 14 differentially expressed proteins that were associated with "Connective Tissue Function". Among them, fibromodulin(FMOD), Collagen alpha-1 (XIV) chain(COL14A1), Calponin-1 (CNN-1), Tenascin (TNC), and Galectin-1(LGALS1 appeared most likely to play a role in the etiology of pelvic organ prolapse. Conclusions and clinical relevence: We identified at least 6 proteins not previously associated with the pathogenesis of pelvic organ prolapse with biologic functions that suggest a plausible relationship to the disorder. These results may be helpful for furthering our understanding of the pathophysiological mechanisms of pelvic organ prolapse.
2018-12-10 | PXD011467 | Pride
Project description:Failure of ligamentous support of the genital tract to resist intra-abdominal pressure is a plausible underlying mechanism for the development of pelvic organ prolapse, but the nature of molecular response of pelvic tissue support remains unknown. We hypothesized that the expression of genes coding for proteins involved in maintaining the cellular and extracellular integrity would be altered in cases of pelvic organ prolapse. Therefore, cDNA microarrays were used to examine the difference in transcriptional profile in RNA of primary culture fibroblasts subjected to mechanical stretch and those that remained static. Keywords: Changes in transcription profile in pelvic organ fibroblasts in response to stretch
2007-01-26 | GSE6862 | GEO