Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury
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ABSTRACT:
PROVIDER: PRJNA802134 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17833961_1.fastq.gz | Fastqsanger.gz | |||
| SRR17833961_2.fastq.gz | Fastqsanger.gz | |||
| SRR17833962_1.fastq.gz | Fastqsanger.gz | |||
| SRR17833962_2.fastq.gz | Fastqsanger.gz | |||
| SRR17833963_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
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Project description:Adult regeneration in spinal cord is poor in mammalian but remarkable in the neonatal mammals and some vertebrates, including fish and salamanders. Increasing evidences basis of this interspecies and ontogeny highlighted the pivotal roles of neuron extrinsic factors-the glial scar, which exert confusing inhibiting or promoting regeneration function, but the spatiotemporal ordering of cellular and molecular events that drive repair processes in scar formation remains poorly understood. Here, we firstly constructed tissue-wide gene expression measurements of mouse spinal cords over the course of scar formation using the spatial transcriptomics (ST) technology in Spinal cord injury (SCI) repair. We analyzed the transcriptomes of nearly 15449 spots from 32 samples and distinguished normal and damage response regions. Compared to histological changes, spatial mapping of differentiation transitions in spinal cord injury site delineated the possible trajectory between subpopulations of fibroblast, glia and immune cell more comprehensively and defined the extent of scar boundary and core more accurately. Locally, we identified gene expression gradients from leading edge to the core of scar areas that allow for re-understanding of the scar microenvironment and found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophage, CD36 and Postn in fibroblast, Plxnb2 and Nxpe3 in microglia, Clu in astrocyte and CD74 in oligodendrocyte. Last, we profiled the bidirectional ligand-receptor interactions at the neighbor cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found GPR37L1_PSAP and GPR37_PSAP were top 2 enriched gene-pairs between microglia and fibroblast or microglia and astrocyte. Together, the establishment of these profiles firstly uncovered scar spatial heterogeneity and lineage trajectory, provide an unbiased view of scar and served as a valuable resource for CNS injury treatment.
2022-02-01 | GSE195783 | GEO
Project description:CNS injury results in chronic scar formation that interferes with function and inhibits repair. Extracellular matrix (ECM) is prominent in the scar and potently regulates cell behavior. However, comprehensive information about the ECM proteome is largely lacking, and region- as well as injury-specific differences are often not taken into account. These aspects are the focus of our perspective on injury and scar formation. To highlight the importance of such comprehensive proteome analysis we include data obtained with novel analysis tools of the ECM composition in the scar and show the contribution of monocytes to the ECM composition after traumatic brain injury (TBI). Monocyte invasion was reduced using the CCR2-/- mouse line and step-wise de-cellularization and proteomics allowed determining monocyte-dependent ECM composition and architecture of the glial scar. We find significant reduction in the ECM proteins Tgm1, Itih (1,2, and 3), and Ftl in the absence of monocyte invasion. We also describe the scar ECM comprising zones with distinctive composition and show a subacute signature upon comparison to proteome obtained at earlier times after TBI. These results are discussed in light of injury-, region- and time-specific regulation of scar formation highlighting the urgent need to differentiate injury conditions and CNS-regions using comprehensive ECM analysis.
2020-05-27 | PXD017478 | Pride
Project description:We performed spatial and single-cell transcriptomics on male mouse brains to map out the molecular and cellular processes governing the response to ischemic stroke during the first week after the injury. Focusing on glial cells, we documented their activation, the formation of the glial scar, and significant changes in cell–cell communication patterns. Interestingly, we identified various activated populations of oligodendrocytes that, while similar in their anti-inflammatory properties, differ in their immunogenic and metabolic characteristics. This challenges the long-held belief that oligodendrocytes play a passive role in neuropathologies. Altogether, we present a major contribution to the current understanding of the role of glial cells in stroke pathobiology, comprehensively mapping their acute response and role in the formation of the glial scar.
2024-11-18 | GSE233814 | GEO
Project description:We performed spatial and single-cell transcriptomics on male mouse brains to map out the molecular and cellular processes governing the response to ischemic stroke during the first week after the injury. Focusing on glial cells, we documented their activation, the formation of the glial scar, and significant changes in cell–cell communication patterns. Interestingly, we identified various activated populations of oligodendrocytes that, while similar in their anti-inflammatory properties, differ in their immunogenic and metabolic characteristics. This challenges the long-held belief that oligodendrocytes play a passive role in neuropathologies. Altogether, we present a major contribution to the current understanding of the role of glial cells in stroke pathobiology, comprehensively mapping their acute response and role in the formation of the glial scar.
2024-11-18 | GSE233813 | GEO
Project description:We performed spatial and single-cell transcriptomics on male mouse brains to map out the molecular and cellular processes governing the response to ischemic stroke during the first week after the injury. Focusing on glial cells, we documented their activation, the formation of the glial scar, and significant changes in cell–cell communication patterns. Interestingly, we identified various activated populations of oligodendrocytes that, while similar in their anti-inflammatory properties, differ in their immunogenic and metabolic characteristics. This challenges the long-held belief that oligodendrocytes play a passive role in neuropathologies. Altogether, we present a major contribution to the current understanding of the role of glial cells in stroke pathobiology, comprehensively mapping their acute response and role in the formation of the glial scar.
2024-11-18 | GSE233812 | GEO
Project description:We performed spatial and single-cell transcriptomics on male mouse brains to map out the molecular and cellular processes governing the response to ischemic stroke during the first week after the injury. Focusing on glial cells, we documented their activation, the formation of the glial scar, and significant changes in cell–cell communication patterns. Interestingly, we identified various activated populations of oligodendrocytes that, while similar in their anti-inflammatory properties, differ in their immunogenic and metabolic characteristics. This challenges the long-held belief that oligodendrocytes play a passive role in neuropathologies. Altogether, we present a major contribution to the current understanding of the role of glial cells in stroke pathobiology, comprehensively mapping their acute response and role in the formation of the glial scar.
2024-11-18 | GSE233811 | GEO
Project description:Pathologies of the central nervous system (CNS) white matter often result in permanent functional deficits because mature mammalian projection neurons fail to regenerate long-distance axons after injury. A major barrier to axonal regenerative research is that the CNS axons that regenerate in response to experimental treatments stall growth before reaching their post-synaptic targets. Here, we test the hypothesis that interaction of regenerating axons with live oligodendrocytes, which were absent during developmental axon growth, stalls axonal growth. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistological analysis to investigate whether post-injury born oligodendrocytes incorporate into the glial scar after optic nerve injury. Then, we administered demyelination-inducing cuprizone (used in studies of multiple sclerosis), concurrently with the stimulation of axon regeneration by Pten knockdown (KD) in projection neurons after optic nerve injury. We found that post-injury born oligodendrocyte lineage cells incorporate into the glial scar, where they are susceptible to the demyelination diet treatment, which reduced their presence in the glial scar. We further found that the demyelination diet enhanced Pten KD-stimulated axon regeneration, and localized injection of cuprizone promoted axon regeneration. We also present a website for comparing the gene expression of scRNA-seq-profiled optic nerve oligodendrocyte lineage cells under physiological and pathophysiological conditions. Annotation of oligodendrocyte lineage cell subtypes, and normal or injured condition, are indicated in the last two rows of the cell matrix CSV file.
2023-03-27 | GSE225410 | GEO
Project description:Scar formation is a major hindrance to central nervous system regeneration upon traumatic injury. Glial cells are key players during the wound healing process, and their reaction to injury determines the extent of tissue restoration. Here, we used the regenerative potential of the zebrafish telencephalon to identify specific molecular and cellular mechanisms regulating glial scar formation. We demonstrated that contact of the cerebrospinal fluid with the brain parenchyma after injury activates toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways leading to initiation of a glial scar. These pathways were critical for scarring even after ablation of microglia and infiltrating monocytes. Our data support a specific role for the injury-induced Tlr1/2 and Cxcr3 signaling pathways in controlling proliferation of the oligodendrocyte progenitors and therefore exacerbated glial reactivity, contributing to scar formation. Interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated glial scar formation and improved tissue restoration.
2022-01-18 | GSE98217 | GEO
Project description:Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
| S-EPMC9905408 | biostudies-literature
Project description:Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia
| PRJNA978030 | ENA