Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fibroblasts orchestrate the pathogenesis of fibrotic and glial scar in spinal cord injury

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE190910 | GEO | 2022/11/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression data of C57BL/6, Il1a-knockout and Il1b-knockout mice at 24 hours after spinal cord injury

Project description:We have previously shown that Il1a-knockout (KO) mice exhibit rapid (at day 1) and persistent improvements in locomotion associated with reduced lesion volume compared with Il1b-KO mice and C57BL/6 controls after traumatic spinal cord injury (SCI). To investigate the mechanism by which Il1a mediates its detrimental effect, we analyzed the transcriptome of the injured spinal cord of Il1a-KO, Il1b-KO and C57BL/6 mice at 24 hours after SCI using GeneChip microarrays. Il1a-KO, Il1b-KO and C57BL/6 mice were subjected to a 50-kdyn SCI and a 6-mm spinal cord segment centered over the site of contusion extracted for RNA isolation and microarray analysis.

2015-06-27 | E-GEOD-70302 | biostudies-arrayexpress

Cellular response of mesenchymal stem cells transplanted into spinal cord injury

Project description:Mesenchymal stem cells (MSCs) and their cellular response to various stimuli have been characterized in great detail in culture conditions. In contrast, the cellular response of MSCs in an in vivo setting is still uncharted territory. In this study, we investigated the cellular response of MSCs following transplantation into spinal cord injury (SCI).Mouse bone marrow-derived MSCs were transplanted 24h following severe contusion SCI in mice. As controls, MSCs transplanted to uninjured spinal cord and non-transplanted MSCs were used. At seven days post transplantation, the MSCs were isolated from the SCI, and their global transcriptional changes investigated using RNA-sequencing. We found that MSCs transplanted into SCI down-regulate their response to cytokines, tendency to adhere and to undergo phagocytosis but up-regulate their ability to repair DNA and proliferate.

2019-04-23 | GSE125176 | GEO

Transcription profiling of moderately injuried mouse spinal cord at different time points after the injury to characterize the temporal changes in gene expression that underlie the secondary injury responses.

Project description:Traumatic spinal cord injury (SCI) initiates a complex series of pathophysiological secondary responses that lead to tissue loss and functional deficits.This study represents a comprehensive database of temporal changes in gene expression that underlie the secondary injury response that occurs in a well-defined mouse model of contusion injury. Experiment Overall Design: Global changes in gene expression that contribute to secondary injury in a C57BL6 mouse model of contusion injury were evaluated using Affymetrix Mouse Genome 430 2.0 arrays.Mice were subjected to a moderate injury at the T8 spinal segment under isoflurane anesthesia.Sections of cord (0.4 cm in length) were analyzed from the site of impact and from the immediately adjacent rostral and caudal regions at 0.5, 4, 24, 72 h and 7 and 28 days after injury (n=3/per group), sham-injury (n=2 per group), or from naive mice (n=2). Four mice were pooled for each individual n, for a total of 12 mice for each injury time point.

2007-11-29 | E-GEOD-5296 | biostudies-arrayexpress

Molecular responses in skeletal muscles following spinal cord injury and the effect of locomotor training

Project description:Spinal cord injury (SCI) is one of the most disabling health problems facing adults today. Locomotor training has been shown to induce substantial recovery in muscle size and muscle function in both transected and contusion injury animal models of SCI. The overall objective of this study is to implement genome wide expression profiling of skeletal muscle to define the molecular pathways associated with muscle remodeling after SCI and during locomotor training (TM). We profiled rat soleus of total 36 samples including controls; 3, 8 and 14 days after SCI; 8 and 14 days after SCI with locomotor treadmill training (TM).

2015-06-30 | E-GEOD-45550 | biostudies-arrayexpress

Molecular responses in skeletal muscles following spinal cord injury and the effect of locomotor training

2015-06-30 | GSE45550 | GEO

Spatiotemporal dynamics of molecular expression pattern and intercellular interactions in glial scar responding to spinal cord injury

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

Homo sapiens

Project description:BMS-470539 on human synovial fibroblasts

| PRJNA385818 | ENA

Differential Expression profiles of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury

Project description:The goals of this study are to screen differential expression profiles of tRNA-Derived small RNAs (tsRNAs) in rats after traumatic spinal cord injury (SCI) using next-generation sequencing and qRT-PCR.As a result, in rat spinal cord 1 day after contusion, totally 297 tsRNAs differentially expressed were identified. 155 tsRNAs were significantly differentially expressed: 91 were significantly up-regulated, while 64 were significantly down-regulated after SCI (folding change>1.5; P<0.05).Next, four tsRNAs were selected to be verified by qRT-PCR. Taken together,this study explored, for the first time, the significant alteration of tsRNA expression profiles after traumatic SCI in rats and offered deep insights into many possible treatment targets of SCI by regulating tsRNAs.

2020-01-24 | GSE133157 | GEO

BMS-470539 on human synovial fibroblasts

Project description:Gene expression profile of BMS-470539 on human synovial fibroblasts.

2019-12-16 | GSE98658 | GEO

Spinal Cord Injury Murine Model

2006-07-12 | GSE5296 | GEO