Differentially expressed ncRNAs derived from circulating exosomes in the pathogenesis of rat spinal cord injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA881343 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21609249_1.fastq.gz | Fastqsanger.gz | |||
| SRR21609249_2.fastq.gz | Fastqsanger.gz | |||
| SRR21609250_1.fastq.gz | Fastqsanger.gz | |||
| SRR21609250_2.fastq.gz | Fastqsanger.gz | |||
| SRR21609251_1.fastq.gz | Fastqsanger.gz |
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Project description:This study was originally designed to have a general overview of differentially expressed ncRNAs including miRNAs, circRNAs and lncRNAs, from circulating exosomes in SCI rats in comparison with the control rats.
2022-11-08 | GSE213561 | GEO
Project description:Spinal cord injury (SCI) remains one kind of devastating neurological damage, and specific molecular mechanisms involved need to be understood deeply. Currently, circular RNAs (circRNAs), as a newly discovered type of non-coding RNAs (ncRNAs), have been under active investigation. Through functional interactions with disease-associated microRNAs (miRNAs), exosome-derived circRNAs have been extensively implicated in various organ pathogenesis. Nevertheless, the functional involvement of circulating circRNAs in SCI onset, progression as well as repair remains poorly explored until now. Of note, there still lacks clinical and experimental evidence in this regard. To obtain some relevant knowledge in this field, this study was originally designed to have a general overview of differentially expressed circRNAs derived from circulating exosomes in SCI rats in comparison with the control rats. It turned out that 709 types of downregulated circRNAs and 346 kinds of upregulated circRNAs were preliminarily screened out. Functional enrichment analyses including kyoto encyclopedia of genes and genomes (KEGG) pathway and gene ontology (GO) were performed to evaluate the possible biological functions of upregulated as well as downregulated circRNAs involved in SCI. Furthermore, five types of upregulated circulating circRNAs including chr4:208359914-208362182+, chr15:20088296-20092102+, chr1:175098934- 175134845-, chr1:175099657- 175128203-, and chr1:175104454- 175134845-, and plus five kinds of downregulated circulating circRNAs including chr11:74154652- 74159524-, chr12:45412398- 45412635-, chr7:137630261- 137648924-, chr6:6280974-6281188+, and chr4:225251864-225254087+, were verified through reverse transcription-polymerase chain reaction (RT-PCR). At last, taking these differentially expressed circRNAs in the center, the circRNA-miRNA-mRNA gene interaction network was constructed to predict the possible functionalities of circRNAs in SCI through anticipating specific interactive miRNAs, giving new insights into how circRNAs contribute to this pathological process. Taken together, these findings suggest the possible involvement and functional significance of circRNAs in SCI.
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Project description:This project is "Phosphoproteomic analysis of the lumbar spinal cord, a lesion site in the amyotrophic lateral sclerosis (ALS) mouse model SOD1G93A mice". The aim of this study is to clarify the phosphorylation changes by the lumbar spinal cord of SOD1G93A mice at 20w by applying proteomics technology. The goal of this study is to better understand the pathogenesis of ALS. lumbar spinal cord of SOD1G93A mice (n=5) and WT mice (n=4) were collected at 20w, and the phosphoproteomics were compared.
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Project description:Spinal cord injury (SCI) remains a devastating neurological disorder with limited treatment options. Among emerging therapeutic strategies, the transplantation of mesenchymal stem cell-derived exosomes (MSC-Exos) has shown great promise owing to their functional consistency with donor cells, low immunogenicity, and suitability for various delivery routes. Wnt5a, a non-canonical Wnt ligand, has been reported to promote neuronal differentiation and spinal cord regeneration. However, its mechanistic role when delivered via exosomes (Exos) remains unclear. In the present study, the function and underlying mechanism of Wnt5a in promoting neuronal differentiation and spinal cord repair were investigated using bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) in both in vitro and in vivo models. Our results demonstrated that Wnt5a-enriched BMSC-Exos significantly enhanced the proliferation and neuronal differentiation of neural stem cells, while suppressing astrocyte formation. High-throughput RNA sequencing revealed an association between Wnt5a and the nuclear factor-kB (NF-kB) signaling pathway. Intervention with lipopolysaccharide confirmed that Wnt5a exerts a suppressive effect on this pathway. In vivo, the transplantation of Wnt5a-modified BMSC-Exos facilitated the polarization of microglia toward an anti-inflammatory M2 phenotype, promoted neurogenesis, reduced astrocyte accumulation, improved spinal cord tissue architecture, and led to better motor function recovery. Collectively, these findings indicate that Wnt5a enhances the neuroregenerative potential of BMSC-Exos by modulating immune responses and suppressing neuroinflammation, likely through inhibiting the NF-kB signaling pathway. This strategy may offer a promising avenue for treating SCI
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Project description:Spinal cord injury (SCI) is a severe neurological dysfunction, and its pathogenesis remains inadequately understood. Here, to spatiotemporally decode the cellular and molecular pathogenesis of SCI, we performed spatial transcriptomics analysis of 12,930 single cells from 21 samples of SCI contusion model mice. We identified the specific cellular subtypes, differentially expressed genes (DEGs), cell signaling networks, site-specific genes (SSGs), and transcription factors involved in SCI. Our analysis indicated that fibroblasts served as the hub of intracellular communication in the SCI site, sent continuous immune signals to neurocytes, and induced the other cell types to express high levels of the fibroblast marker gene Col1a2. Pseudotime analysis visualized trajectories that emerged from fibroblasts, passed through microglia and ended at neurons after SCI. When the proportion of fibroblasts and their cellular communications were attenuated by solu-medrol treatment, the BMS and MEP performance of SCI mice increased significantly; moreover, the ratio of Col1a2+ cells decreased markedly, and a new subtype of fibroblasts expressing Arg1 appeared. Our results highlight the vital pathological position of fibroblasts and indicate it as a significant therapeutic target for SCI.
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