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:Single-cell RNA sequencing of neurogenic bladder resulting from pelvic nerve injury in rats
| PRJNA1308537 | ENA
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:Purpose: This study aimed to investigate the imaging characteristics and molecular mechanisms by which pelvic floor electrical stimulation (PFES) improves pelvic floor muscle injury in a rat model of stress urinary incontinence (SUI). Methods: An SUI model was established in female Sprague-Dawley rats via vaginal distension combined with bilateral ovariectomy. One week post-modeling, the stimulation group received intravaginal PFES for 2 weeks. Evaluations included 9.4 T MRI, urodynamic tests, histopathological staining, qPCR, Western blotting, and RNA-seq. Results: PFES significantly elevated ALPP compared with controls, indicating improved urinary continence. MRI demonstrated that PFES attenuated focal hyperintensity, muscle edema, and fiber disorganization in the pubococcygeus muscle. Histological analyses confirmed that PFES restored dense muscle fiber arrangement and collagen distribution, and immunohistochemistry showed upregulated expression of COL1A1, COL3A1, and CD34. RNA-seq revealed that differentially expressed genes were prominently enriched in ECM organization, focal adhesion, ECM-receptor interaction, and the PI3K-Akt pathway. Western blotting verified that PFES increased COL1A1, COL3A1, and VEGFA, while suppressing the atrophy-related ubiquitin ligase FBXO32. Conclusion: PFES effectively repairs pelvic floor muscle structure and function by reducing muscle edema and fiber disruption, upregulating type I and III collagens to promote ECM remodeling, inducing VEGF-mediated angiogenesis, and downregulating FBXO32 to counteract atrophy. These findings elucidate PFES mechanisms and support its clinical application.
2026-08-13 | GSE343122 | 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:Kidney fibrosis is a major hallmark of chronic kidney disease and is defined by an excessive accumulation of extracellular matrix, primarily collagens. While collagen synthesis has been extensively investigated, the contribution of impaired collagen degradation to the development of fibrosis remains poorly understood. Collagen degradation involves the activity of proteases producing collagen-derived peptides (CDPs). Here we tested the hypothesis whether reduced collagen degradation participates to the development of kidney fibrosis. For that, CDPs were quantified in pelvic urine of kidney undergoing fibrosis following unilateral ureteral obstruction (UUO). C57Bl6 male mice underwent UUO- or sham-surgery and were sacrificed after 3- or 7-days (3D or 7D). Fibrosis was evaluated by histology. Urinary CDP composition (qualitative-sequences and quantitative-abundances) was analysed by mass spectrometry (MS). Based on collagen protein deposition, UUO-induced fibrosis was detected at 7D and not at 3D. At both 3D and 7D, of the more than 300 significantly different CDPs were found in UUO-pelvic urine, 70% of them displaying a reduced abundance in UUO compared to sham-bladder. In UUO-bladder urine, significant CDPs were found only at 7D with 79% of them displaying increased abundance. CDPs derived from Col1a1, Col1a2 and Col3a1 were the most represented and distributed in clusters along their parental protein sequence. Most clusters were composed of seemingly decreasing length CDPs containing the entire sequence of the shortest CDP. Within the clusters, inter-CDP correlations of abundance were very different between UUO-pelvis and UUO-bladder at 3D and 7D post-UUO. In conclusion, using a mouse model of fibrosis that enables the specific study of CDPs from the fibrotic kidney, we observe that reduced collagen degradation could play a key role in the early stages of fibrosis development. Our research suggests a potential need for a shift in the development of anti-fibrotic strategies, emphasizing not only the inhibition of collagen synthesis but also the enhancement of its degradation.
2026-01-12 | PXD064569 | Pride
Project description:Pelvic autonomic nerve injury is a major cause of postoperative bowel dysfunction, yet effective strategies for restoring damaged pelvic ganglia remain lacking. Here, we demonstrate that extracellular vesicles derived from human pluripotent stem cell–induced sacral neural crest cells (Sacral NC-EVs) promote pelvic neuroregeneration by suppressing oxidative stress–induced pyroptosis. In a rat model of major pelvic ganglion (MPG) injury, local administration of Sacral NC-EVs improved gastrointestinal motility and partially restored rectal neural innervation and epithelial barrier integrity. Mechanistically, MPG injury induced a hypoxia-associated oxidative microenvironment that activated the NLRP3–caspase-1–GSDMD pyroptosis pathway, whereas Sacral NC-EVs effectively attenuated oxidative stress and inhibited pyroptotic signaling. Comparative analyses showed that Sacral NC-EVs produced more pronounced overall therapeutic effects than mesenchymal stem cell–derived and vagal neural crest–derived EVs, highlighting a functional advantage of developmental lineage matching. Proteomic and functional studies identified annexin A1 (ANXA1) as an important EV-associated mediator that acts through FPR2 signaling to contribute to the antioxidant and anti-pyroptotic effects of Sacral NC-EVs. Collectively, our findings establish lineage-matched EVs as a mechanism-driven, cell-free strategy for neural repair by targeting the oxidative stress–pyroptosis axis.
2026-07-31 | GSE338995 | GEO
Project description:Healthy pelvic floor muscles (PFMs) are essential for proper pelvic floor function. The biggest risk factor for PFM dysfunction is injury sustained during vaginal childbirth, yet the factors that facilitate or impair PFM recovery from birth injury remain unknown. We aimed to assess the impact of the postpartum milieu in the presence and absence of lactation on PFM regeneration following simulated birth injury (SBI) in a pregnant rat model. We determined that lactating rats have a rapid increase in systemic immune markers in response to SBI, which contributes to rapid changes in PFM immune cell infiltration and decrease in pro-inflammatory genes. PFMs in lactating rats have enrichment of anti-inflammatory genes and larger newly formed myofibers that contribute to larger myofiber size after weaning. This suggests that lactation promotes an earlier anti-inflammatory response in injured PFMs that allows for quicker myogenesis and myofiber hypertrophy.
2026-07-15 | GSE328667 | 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 |