Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A spatiotemporal molecular atlas of mouse spinal cord injury identifies a distinct astrocyte subpopulation and therapeutic potential of IGFBP2

ABSTRACT: Spinal cord injury (SCI) triggers a cascade of intricate molecular and cellular changes that determine the outcome. In this study, we resolve the spatiotemporal organization of the injured mouse spinal cord and quantitatively assess in situ cell-cell communication following SCI. By analyzing existing single-cell RNA-sequencing datasets alongside our spatial data, we delineate a subpopulation of Igfbp2-expressing astrocytes that migrate from the white matter (WM) to grey matter (GM) and become reactive upon SCI, termed as Astro-GMii. Further, Igfbp2 upregulation promotes astrocyte migration, proliferation and reactivity, and the secreted IGFBP2 protein fosters neurite outgrowth. Finally, we show that IGFBP2 significantly reduces neuronal loss and remarkably improves the functional recovery in a mouse model of SCI in vivo. Together, this study not only provides a comprehensive molecular atlas of SCI but also exemplifies how the rich resource can be applied to endow cells and genes with functional insight and therapeutic potential.

ORGANISM(S): Mus musculus

PROVIDER: GSE256397 | GEO | 2024/06/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Small Extracellular Vesicles derived from four dimensional-culture of mesenchymal stem cells induce alternatively activated macrophages by upregulating IGFBP2/EGFR to attenuate inflammation in the spinal cord injury of rats

Project description:Effectively reducing the inflammatory response after spinal cord injury (SCI) is a challenging clinical problem and the subject of active investigation. This study employed a porous scaffold-based three dimensional long-term culture technique to obtain human umbilical cord mesenchymal stem cell (hUC-MSC)-derived Small Extracellular Vesicles (sEVs) (three dimensional culture over time, the “4D-sEVs”). Moreover, the vesicle size, number, and inner protein concentrations of the MSC 4D-sEVs contained altered protein profiles compared with those derived from 2D culture conditions. A proteomics analysis suggested broad changes, especially significant upregulation of Epidermal Growth Factors Receptor (EGFR) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2) in 4D-sEVs compared with 2D-sEVs. The endocytosis of 4D-sEVs allowed for the binding of EGFR and IGFBP2, leading to downstream STAT3 phosphorylation and IL-10 secretion and effective induction of macrophages/microglia polarization from the pro-inflammatory M1 to anti-inflammatory M2 phenotype, both in vitro and in the injured areas of rats with compressive/contusive SCI. The reduction in neuroinflammation after 4D-sEVs delivery to the injury site epicenter led to significant neuroprotection, as evidenced by the number of surviving spinal neurons. Therefore, applying this novel 4D culture-derived Small Extracellular Vesicles could effectively curb the inflammatory response and increase tissue repair after SCI.

2023-07-20 | PXD040516 | Pride

Mass spectrometry imaging analysis of traumatic spinal cord

Project description:To comprehensively elucidate metabolite changes in different anatomical structures (e.g., gray matter and white matter) after spinal cord injury(SCI), our study utilized air-flow-assisted desorption electrospray ionization mass spectrometry imaging platforms to perform untargeted metabolomic studies. These analyzes are designed to identify metabolites critical in spinal cord injury. confirmed the profile differences in white and gray matter as well as in ventral and dorsal horns after SCI. These results provide valuable information for understanding in situ metabolite alterations after SCI.

2025-03-28 | PXD060179 | Pride

Divergent transcriptional regulation of astrocyte reactivity across disorders [TR_ATAC_SCI]

Project description:Single-nuclei Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) was applied to examine chromatin landscape changes and transcriptional regulator (TR) DNA motif accessibility in reactive astrocytes following traumatic spinal cord injury (SCI). Astrocyte nuclei were isolated from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case TRs, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Comparison of differential chromatin accessibility revealed substantial remodeling during astrocyte reactivity, with more chromatin opening than closing. Marked alterations in access to SCI reactivity-associated TR motifs were also detected.

2022-05-26 | GSE199481 | GEO

Divergent transcriptional regulation of astrocyte reactivity across disorders [RNA-seq]

Project description:RNA sequencing was applied to examine changes in gene expression in reactive astrocytes following traumatic spinal cord injury (SCI) or neuroinflammatory insult by systemic administration of lipopolysaccharide (LPS). Transgenic Ribotag technology was used to isolate astrocyte ribosome-associated mRNAs from the spinal cord of wild type mice and mice with astrocyte-specific conditional gene deletion (cKO) of test-case transcriptional regulators of reactivity, SMARCA4 (Smarca4-astro-cKO) or STAT3 knockout (Stat3-astro-cKO). Examination of differentially expressed gene (DEG) profiles by upstream transcriptional regulator enrichment analysis (TREA) was used identify transcriptional regulators of reactivity in each condition. Together, findings from this study show that transcriptional changes associated with astrocyte reactivity are exquisitely heterogeneous and are customized from vast numbers of potential DEGs via context-specific combinatorial TR interactions. These data have also been made accessible in a open-access, searchable database: http://tr.astrocytereactivity.com

2022-05-26 | GSE199149 | GEO

Transcriptome response to endoplasmic reticulum stress in rat oligodendrocyte precursor cells

Project description:In the US, there are approximately 12,000 new cases of traumatic spinal cord injury (SCI) each year. Currently there are no neuroprotective treatments to improve outcome of SCI. Our previous research has revealed that endoplasmic reticulum stress response (ERSR) is an important contributor to oligodendrocyte death and subsequent white matter loss and locomotor impairment after contusive spinal cord injury in mice. ERSR affects activity of multiple transcription factors regulating either pro-survival- or apoptosis-promoting genes. Therefore, we characterized transcriptomic changes in ERSR-challenged oligodendrocytes as a first step to identify new targets for therapies that may attenuate their loss after SCI.

2022-05-15 | GSE81792 | GEO

MHC-II immunopeptidome for CNS injury model

Project description:In homeostasis, because of the blood-brain barrier, immune cells rarely infiltrate the central nervous system (CNS). However, after spinal cord injury (SCI), many cells, including both myeloid and T cells, infiltrate the spinal cord. However, the role immune cells play in SCI remains controversial. We are curious whether after SCI there are self-peptides that are released and sensed by T cells that then modulate response to CNS injury.

2023-01-24 | MSV000091130 | MassIVE

Transcription profiling time series of Rattus norvegicus raphe magnus and sensorimotor cortex samples following moderate spinal cord injury

Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Analysis of the areas directly (spinal cord) and indirectly (raphe and sensorimotor cortex) affected by injury will help understanding mechanisms of SCI. Hypothesis: Areas of the brain primarily affected by spinal cord injury are the Raphe and the Sensorimotor cortex thus gene expression profiling these two areas might contribute understanding the mechanisms of spinal cord injury. Specific Aim: The project aims at finding significantly altered genes in the Raphe and Sensorimotor cortex following an induced moderate spinal cord injury in T9.

2007-10-08 | E-GEOD-2270 | biostudies-arrayexpress

Transcription profiling time series analyzing the molecular events in rat spinal cord sections following mechanical injury

Project description:Summary: Spinal cord injury (SCI) is a damage to the spinal cord induced by trauma or disease resulting in a loss of mobility or feeling. SCI is characterized by a primary mechanical injury followed by a secondary injury in which several molecular events are altered in the spinal cord often resulting in loss of neuronal function. Hypothesis: Spinal cord injury (SCI) induces a cascade of molecular events including the activation of genes associated with transcription factors, inflammation, oxidative stress, ionic imbalance, apoptosis and neuroregeneration which suggests the existance of endogenous reparative attempts. However, not all mechanisms following SCI are well known. Specific Aim: The goal of this project is to analyze the molecular events following spinal cord injury 1 cm above, below, and at the site of injury (T9), aiming at finding potential new targets to improve recovery and therapy.

2007-09-04 | E-GEOD-464 | biostudies-arrayexpress

Spinal Cord Trauma Supraspinal Tracts

2005-02-11 | GSE2270 | GEO

Single nucleus RNAseq of mouse astrocytes after traumatic spinal cord injury

Project description:We conducted snRNAseq of mouse astrocytes after traumatic spinal cord injury (SCI). These data reveal transcriptomic similarities and differences among astrocytes in healthy spinal cord and after spinal cord injury.

2024-01-09 | GSE247844 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data