Similar Datasets
Project description:The decellularized spinal cord matrix (DSCM) provides the advantage in the translational potential for microenvironment replacement therapies to repair spinal cord injury (SCI) However, the cell type alteration in the SCI repairing niche is undefined. Using single cell transcriptome and bulk RNA-seq analysis, we showed that DSCM regulated cell fate changes in niches related to the multicellular model. This work opens the door for understanding the SCI repairing from a tissue niche perspective.
2022-12-31 | GSE202731 | GEO
Project description:Decellularized Spinal Cord Matrix Manipulate Glial Niche Alteration via Serglycin Mediated Signalling Pathway
| PRJNA837176 | ENA
Project description:Decellularized Spinal Cord Matrix Manipulate Glial Niche Alteration via Serglycin Mediated Signalling Pathway [scRNA-seq]
| PRJNA842511 | ENA
Project description:Astrocytes are the most abundant and widespread glial cells in the central nervous system. The heterogeneity of astrocytes plays an essential role in spinal cord injury (SCI) repair. Decellularised spinal cord matrix (DSCM) is advantageous for repairing SCI, but little is known regarding the exact mechanisms and niche alterations. Here, we investigated the DSCM regulatory mechanism of glial niche in the neuro-glial-vascular unit using single-cell RNA sequencing. Our single cell sequencing, molecular and biochemical experiments validated that DSCM facilitated the differentiation of neural progenitor cells through increasing the number of immature astrocytes. Upregulation of mesenchyme-related genes, which maintained astrocyte immaturity, causing insensitivity to inflammatory stimuli. Subsequently, we identified serglycin (SRGN) as a functional component of DSCM, which involves inducing CD44-AKT signalling to trigger human spinal cord-derived primary astrocytes (hspASCs) proliferation and upregulation of genes related to epithelial-mesenchymal transition, thus impeding astrocyte maturation. Finally, we verified that SRGN-COLI and DSCM had similar functions in the human primary cell co-culture system to mimic the glia niche. In conclusion, our work revealed that DSCM reverted astrocyte maturation and altered the glia niche into the repairing phase through the SRGN-mediated signalling pathway.
| S-EPMC10472524 | biostudies-literature
Project description:Glial scarring following severe tissue damage and inflammation after spinal cord injury (SCI) is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI.
| S-EPMC5561940 | biostudies-other
Project description:Recent studies showed that RNA N6-methyladenosine (m6A) plays an important role in neurological diseases. We used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) technology to generate the m6A modification map after traumatic spinal cord injury (TSCI). A total of 2,609 differential m6A peaks were identified after TSCI. Our RNA sequencing results after TSCI showed 4,206 genes with significantly altered expression. Cross-link analysis of m6A sequencing results and RNA sequencing results showed that 141 hyper-methylated genes were upregulated, 53 hyper-methylated genes were downregulated, 57 hypo-methylated genes were upregulated, and 197 hypo-methylated genes were downregulated. Among these, the important inflammatory response factor Tlr4 and the important member of the neurotrophin family Ngf were both upregulated and hyper-methylated after TSCI. This study provides that in the future, the epigenetic modifications of the genes could be used as an indicator of TSCI.
| S-EPMC9189298 | biostudies-literature
Project description:After spinal cord injury (SCI), a fibrotic scar forms at the injury site that is best characterized by the accumulation of perivascular fibroblasts and deposition of the extracellular matrix protein fibronectin. While fibronectin is a growth-permissive substrate for axons, the fibrotic scar is inhibitory to axon regeneration. The mechanism behind how fibronectin contributes to the inhibitory environment and how the fibronectin matrix is assembled in the fibrotic scar is unknown. By deleting fibronectin in myeloid cells, we demonstrate that fibroblasts are most likely the major source of fibronectin in the fibrotic scar. In addition, we demonstrate that fibronectin is initially present in a soluble form and is assembled into a matrix at 7 d post-SCI. Assembly of the fibronectin matrix may be mediated by the canonical fibronectin receptor, integrin α5β1, which is primarily expressed by activated macrophages/microglia in the fibrotic scar. Despite the pronounced cavitation after rat SCI, fibrotic scar also is observed in a rat SCI model, which is considered to be more similar to human pathology. Taken together, our study provides insight into the mechanism of fibrotic scar formation after spinal cord injury.
| S-EPMC4507358 | biostudies-literature
Project description:In mammals, spinal cord injury results in permanent sensory-motor loss due in part to a failure in reinitiating local neurogenesis. However, zebrafish show robust neuronal regeneration and functional recovery even after complete spinal cord transection. Postembryonic neurogenesis is dependent upon resident multipotent progenitors, which have been identified in multiple vertebrates. One candidate cell population for injury repair expresses Dbx1, which has been shown to label multipotent progenitors in mammals. In this study, we use specific markers to show that cells expressing a dbx1a:GFP reporter in the zebrafish spinal cord are radial glial progenitors that continue to generate neurons after embryogenesis. We also use a novel larval spinal cord transection assay to show that dbx1a:GFP(+) cells exhibit a proliferative and neurogenic response to injury, and contribute newly-born neurons to the regenerative blastema. Together, our data indicate that dbx1a:GFP(+) radial glia may be stem cells for the regeneration of interneurons following spinal cord injury in zebrafish.
| S-EPMC4038170 | biostudies-literature
Project description:BackgroundTransplantation of embryonic stem or neural progenitor cells is an attractive strategy for repair of the injured central nervous system. Transplantation of these cells alone to acute spinal cord injuries has not, however, resulted in robust axon regeneration beyond the sites of injury. This may be due to progenitors differentiating to cell types that support axon growth poorly and/or their inability to modify the inhibitory environment of adult central nervous system (CNS) injuries. We reasoned therefore that pre-differentiation of embryonic neural precursors to astrocytes, which are thought to support axon growth in the injured immature CNS, would be more beneficial for CNS repair.ResultsTransplantation of astrocytes derived from embryonic glial-restricted precursors (GRPs) promoted robust axon growth and restoration of locomotor function after acute transection injuries of the adult rat spinal cord. Transplantation of GRP-derived astrocytes (GDAs) into dorsal column injuries promoted growth of over 60% of ascending dorsal column axons into the centers of the lesions, with 66% of these axons extending beyond the injury sites. Grid-walk analysis of GDA-transplanted rats with rubrospinal tract injuries revealed significant improvements in locomotor function. GDA transplantation also induced a striking realignment of injured tissue, suppressed initial scarring and rescued axotomized CNS neurons with cut axons from atrophy. In sharp contrast, undifferentiated GRPs failed to suppress scar formation or support axon growth and locomotor recovery.ConclusionPre-differentiation of glial precursors into GDAs before transplantation into spinal cord injuries leads to significantly improved outcomes over precursor cell transplantation, providing both a novel strategy and a highly effective new cell type for repairing CNS injuries.
| S-EPMC1561531 | biostudies-literature
Project description:Glial cell types were classified less than 100 years ago by del Rio-Hortega. For instance, he correctly surmised that microglia in pathologic central nervous system (CNS) were "voracious monsters" that helped clean the tissue. Although these historical predictions were remarkably accurate, innovative technologies have revealed novel molecular, cellular, and dynamic physiologic aspects of CNS glia. In this review, we integrate recent findings regarding the roles of glia and glial interactions in healthy and injured spinal cord. The three major glial cell types are considered in healthy CNS and after spinal cord injury (SCI). Astrocytes, which in the healthy CNS regulate neurotransmitter and neurovascular dynamics, respond to SCI by becoming reactive and forming a glial scar that limits pathology and plasticity. Microglia, which in the healthy CNS scan for infection/damage, respond to SCI by promoting axon growth and remyelination-but also with hyperactivation and cytotoxic effects. Oligodendrocytes and their precursors, which in healthy tissue speed axon conduction and support axonal function, respond to SCI by differentiating and producing myelin, but are susceptible to death. Thus, post-SCI responses of each glial cell can simultaneously stimulate and stifle repair. Interestingly, potential therapies could also target interactions between these cells. Astrocyte-microglia cross-talk creates a feed-forward loop, so shifting the response of either cell could amplify repair. Astrocytes, microglia, and oligodendrocytes/precursors also influence post-SCI cell survival, differentiation, and remyelination, as well as axon sparing. Therefore, optimizing post-SCI responses of glial cells-and interactions between these CNS cells-could benefit neuroprotection, axon plasticity, and functional recovery.
| S-EPMC6095774 | biostudies-literature