Differentially expressed ncRNAs derived from circulating exosomes in the pathogenesis of rat spinal cord injury
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ABSTRACT:
PROVIDER: PRJNA881343 | ENA |
REPOSITORIES: ENA
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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.
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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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Project description:Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, which shows that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene, Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis after spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals. Spinal cord injury or control sham injury was performed on adult zebrafish. After 4, 12, or 264 hrs, a 5 mm segment of spinal cord was dissected and processed (as a pool from 5 animals) in three replicate groups for each time point and treatment.
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Project description:Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, which shows that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene, Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis after spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals.
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Project description:Label-free mass spectrometry-based quantitative proteomics was applied to a larval zebrafish spinal cord injury model, which allows axon regeneration and functional recovery within two days (days post lesion; dpl) after a spinal cord transection in 3 day-old larvae (dpf). Proteomic profiling of the lesion site was performed at 1 dpl and 2 dpl as well as corresponding age-matched unlesioned control tissue (4 dpf as control for 1 dpl; 5 dpf as control for 2 dpl).
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