
DOI . ORG {
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Title[redir]:
Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis | Journal of Translational Medicine | Full Text
Description:
Background Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear. Methods Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371. Protein–protein interaction and microRNA-mRNA-transcription factor regulatory networks were constructed based on Search Tool for the Retrieval of Interacting Genes (STRING) and NetworkAnalyst, respectively, which were validated by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Cell subclusters and unique features of microglia in SCI were identified by single-cell transcriptomic analysis, which were validated in GSE226286. Spatial expression patterns of DETIRGs and DEFIRGs were validated in brain injury (GSE214349) and SCI (GSE184369). Potential mechanisms underlying neuronal regeneration by neurotrophin-3 (NT3)-chitosan were revealed by transcriptomic analyses in GSE69334. Immune- and ferroptosis-related mechanisms of nanolayered double hydroxide loaded with NT3 (LDH-NT3) were investigated in vivo and in vitro. Results GBP2, TEC, UNC93B1, PLXNC1, NFATC1, IL10RB, and TLR8 were DETIRGs represented chronic SCI-specific genes and peripheral blood biomarkers. NFKB1 may regulate expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, establishing links between microglial ferroptosis and neuroinflammation. Reduced inflammatory responses and microglial ferroptosis were potential effects of NT3-chitosan or LDH-NT3 on neuronal regeneration. Conclusions A novel subcluster of microglia exhibiting M1 polarization and ferroptosis phenotype was involved in SCI. These microglia may trigger neuroinflammation and induce neuronal degeneration within the middle site of SCI, which might be inhibited by NT3-chitosan or LDH-NT3.
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Keywords {🔍}
sci, microglia, pubmed, cell, article, google, scholar, expression, fig, spinal, analysis, cord, genes, gse, cells, cas, identified, gene, injury, central, ferroptosis, data, immune, defirgs, detirgs, samples, hmox, based, degs, showed, expressed, mice, cybb, group, cellular, database, spatial, molecular, control, wang, differentially, receptor, markers, signaling, potential, subcluster, responses, network, subclusters, tlr,
Topics {✒️}
neural-stem-cell-mediated regenerative medicine pe-conjugated anti-cd11b + antibody poly-l-lysine coated plates mirna-tf-gene regulatory networks anti-pe antibody conjugated e-stained brain sections mirna-mrna-tf regulatory network mirna-mrna-tf interaction network constructing tf-mirna-mrna networks microrna-mrna-tf regulation networks region-specific ferroptosis-related alterations discussion availability single-cell sequencing platforms disease amyloid pathology microrna-mrna-tf networks long-term continued damages springer nature methods data collection fire-polished pasteur pipettes spermidine/spermine n1-acetyltransferase 1 chemotactic factor-induced recruitment single-cell transcriptomic profiling oxygen free-radical injury tf-mirna-gene networks potential references discovering hematoma-stimulated circuits ain-76a control diet cns pathology history mirna-mrna-tf network activating pro-apoptotic factors bmp-smad signaling pathway b-cell antigen receptor stromal cell-derived factor-1 reconstruct cell-developmental trajectories gene-mirna interaction analysis blood rna-seq dataset central nervous system single-cell transcriptomic analysis robust multi-array average specific small-molecular inhibitors oxysterols receptor lxr-alpha mirna-detirg-transcription factor org/web/packages/wgcna/index immune-related pathological mechanisms mirna-defirg-transcription factor k-means clustering analysis stability-related stability correlation bulk rna-seq 3-round microglia depletion-repopulationmice
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headline:Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis
description:Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear. Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371. Protein–protein interaction and microRNA-mRNA-transcription factor regulatory networks were constructed based on Search Tool for the Retrieval of Interacting Genes (STRING) and NetworkAnalyst, respectively, which were validated by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Cell subclusters and unique features of microglia in SCI were identified by single-cell transcriptomic analysis, which were validated in GSE226286. Spatial expression patterns of DETIRGs and DEFIRGs were validated in brain injury (GSE214349) and SCI (GSE184369). Potential mechanisms underlying neuronal regeneration by neurotrophin-3 (NT3)-chitosan were revealed by transcriptomic analyses in GSE69334. Immune- and ferroptosis-related mechanisms of nanolayered double hydroxide loaded with NT3 (LDH-NT3) were investigated in vivo and in vitro. GBP2, TEC, UNC93B1, PLXNC1, NFATC1, IL10RB, and TLR8 were DETIRGs represented chronic SCI-specific genes and peripheral blood biomarkers. NFKB1 may regulate expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, establishing links between microglial ferroptosis and neuroinflammation. Reduced inflammatory responses and microglial ferroptosis were potential effects of NT3-chitosan or LDH-NT3 on neuronal regeneration. A novel subcluster of microglia exhibiting M1 polarization and ferroptosis phenotype was involved in SCI. These microglia may trigger neuroinflammation and induce neuronal degeneration within the middle site of SCI, which might be inhibited by NT3-chitosan or LDH-NT3.
datePublished:2025-01-11T00:00:00Z
dateModified:2025-01-11T00:00:00Z
pageStart:1
pageEnd:28
license:http://creativecommons.org/licenses/by-nc-nd/4.0/
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keywords:
Spinal cord injury
Microglia
Ferroptosis
Immune responses
Single-cell RNA sequencing
Biomaterial
Biomedicine
general
Medicine/Public Health
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headline:Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis
description:Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear. Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371. Protein–protein interaction and microRNA-mRNA-transcription factor regulatory networks were constructed based on Search Tool for the Retrieval of Interacting Genes (STRING) and NetworkAnalyst, respectively, which were validated by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Cell subclusters and unique features of microglia in SCI were identified by single-cell transcriptomic analysis, which were validated in GSE226286. Spatial expression patterns of DETIRGs and DEFIRGs were validated in brain injury (GSE214349) and SCI (GSE184369). Potential mechanisms underlying neuronal regeneration by neurotrophin-3 (NT3)-chitosan were revealed by transcriptomic analyses in GSE69334. Immune- and ferroptosis-related mechanisms of nanolayered double hydroxide loaded with NT3 (LDH-NT3) were investigated in vivo and in vitro. GBP2, TEC, UNC93B1, PLXNC1, NFATC1, IL10RB, and TLR8 were DETIRGs represented chronic SCI-specific genes and peripheral blood biomarkers. NFKB1 may regulate expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, establishing links between microglial ferroptosis and neuroinflammation. Reduced inflammatory responses and microglial ferroptosis were potential effects of NT3-chitosan or LDH-NT3 on neuronal regeneration. A novel subcluster of microglia exhibiting M1 polarization and ferroptosis phenotype was involved in SCI. These microglia may trigger neuroinflammation and induce neuronal degeneration within the middle site of SCI, which might be inhibited by NT3-chitosan or LDH-NT3.
datePublished:2025-01-11T00:00:00Z
dateModified:2025-01-11T00:00:00Z
pageStart:1
pageEnd:28
license:http://creativecommons.org/licenses/by-nc-nd/4.0/
sameAs:https://doi.org/10.1186/s12967-025-06095-0
keywords:
Spinal cord injury
Microglia
Ferroptosis
Immune responses
Single-cell RNA sequencing
Biomaterial
Biomedicine
general
Medicine/Public Health
image:
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