Dynamic astrocytic gene expression profiles after ischemic stroke
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA997998 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25403062_1.fastq.gz | Fastqsanger.gz | |||
| SRR25403062_2.fastq.gz | Fastqsanger.gz | |||
| SRR25403063_1.fastq.gz | Fastqsanger.gz | |||
| SRR25403063_2.fastq.gz | Fastqsanger.gz | |||
| SRR25403064_1.fastq.gz | Fastqsanger.gz |
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Project description:Analysis of astrocytic gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying astrocytic activation after ischemic stroke.
2024-05-23 | GSE238125 | GEO
Project description:Ischemic stroke is a brain injury caused by the occlusion of blood vessels, leading to reduced blood flow, excessive oxidative stress, and the cascade of events, including the formation of the glial barrier, fibrotic scar, neuronal death, and motor impairment. Despite extensive research into stroke etiology, the specific initiation trigger for neuronal death is mainly unknown, severely limiting the development of effective treatments. Here, we demonstrate that excessive H2O2 generation is the initiating factor of ischemic stroke in the photo-thrombosis (PT) mouse and non-human primate (NHP) models, with H2O2-induced astrocytic type I collagen (COL1) playing a crucial role in the cascade of stroke pathology. Treatment with KDS12025, an H2O2-decomposing peroxidase enhancer, significantly alleviates these effects by reducing H2O2-induced COL1 in extremely low doses in mouse and NHP stroke models. In cultured astrocytes, H2O2 stimulates the production of astrocytic COL1 through post-transcriptional up-regulation of Col1 mRNA by decreasing microRNA29, leading to the death of neighboring neurons. Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), we observe profound alterations in N-glycan profiles, particularly fucosylated N-glycans, which reverted to normal levels in both the KDS12025 treatment and astrocytic Col1 gene-silencing groups. The gene-silencing of astrocytic Col1 or Fut8, a key enzyme responsible for core fucosylation necessary for COL1 secretion, prevents neuronal death and motor impairment. Our findings reveal that H2O2-induced astrocytic COL1 production is critical to ischemic stroke. These findings propose that targeting H2O2, astrocytic COL1, and FUT8 could be effective therapeutic strategies for ischemic stroke, offering new avenues for treatment.
2026-03-27 | GSE277625 | GEO
Project description:Ischemic stroke is a brain injury caused by the occlusion of blood vessels, leading to reduced blood flow, excessive oxidative stress, and the cascade of events, including the formation of the glial barrier, fibrotic scar, neuronal death, and motor impairment. Despite extensive research into stroke etiology, the specific initiation trigger for neuronal death is mainly unknown, severely limiting the development of effective treatments. Here, we demonstrate that excessive H2O2 generation is the initiating factor of ischemic stroke in the photo-thrombosis (PT) mouse and non-human primate (NHP) models, with H2O2-induced astrocytic type I collagen (COL1) playing a crucial role in the cascade of stroke pathology. Treatment with KDS12025, an H2O2-decomposing peroxidase enhancer, significantly alleviates these effects by reducing H2O2-induced COL1 in extremely low doses in mouse and NHP stroke models. In cultured astrocytes, H2O2 stimulates the production of astrocytic COL1 through post-transcriptional up-regulation of Col1 mRNA by decreasing microRNA29, leading to the death of neighboring neurons. Using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), we observe profound alterations in N-glycan profiles, particularly fucosylated N-glycans, which reverted to normal levels in both the KDS12025 treatment and astrocytic Col1 gene-silencing groups. The gene-silencing of astrocytic Col1 or Fut8, a key enzyme responsible for core fucosylation necessary for COL1 secretion, prevents neuronal death and motor impairment. Our findings reveal that H2O2-induced astrocytic COL1 production is critical to ischemic stroke. These findings propose that targeting H2O2, astrocytic COL1, and FUT8 could be effective therapeutic strategies for ischemic stroke, offering new avenues for treatment.
2026-03-27 | GSE276260 | GEO
Project description:Dynamic microglial gene expression profiles after ischemic stroke
| PRJNA723336 | ENA
Project description:Analysis of microglial gene expression profiles after ischemic stroke. Stroke is a complicated disease caused by the interaction of multiple celltypes. Results provide new insights into the molecular mechanisms underlying microglial activation after ischemic stroke.
2022-01-01 | GSE172456 | GEO
Project description:Roles of reactive perivascular astrocytes in dysregulation of the blood-brain barrier (BBB) function and cerebral perfusion are not well defined. Here, we investigated transformation of reactive astrocyte function for vascular repair after ischemic stroke by targeted deletion of astrocytic Na+/H+ exchanger isoform 1 in Gfap-CreERT2+/-;Nhe1f/f (Nhe1 Astro-KO) mice. Control Gfap-CreERT2+/-;Nhe1f/f (wild-type) mice displayed BBB damage (elevated endothelial transcytosis and intracellular vesicles) and persistent cerebral hypoperfusion in an ischemic stroke model (transient middle cerebral artery occlusion). In contrast, Nhe1 Astro-KO mice exhibited significantly less endothelial transcytosis and vesicle formation, and increased angiogenesis and cerebral blood perfusion (CBF) post-stroke. Bulk RNA-sequencing transcriptome analysis of isolated GFAP+ reactive astrocytes from wild-type and Nhe1 Astro-KO ischemic brains revealed that ~177 genes were differentially upregulated, with the Wnt7a mRNA among the top upregulated genes, along with additional Wnt pathway genes (Wnt7b, Fzd9, Fzd10, and Ndp). Abundant Wnt7a/b and β-catenin protein expression was detected in cerebral vessels of Nhe1 Astro-KO ischemic brains but not in the wild-type brains. Selective activation of Wnt/β-catenin pathway in cerebral vessels of Nhe1 Astro-KO ischemic brains was further validated using the Wnt reporter line TCF/LEF::H2B-eGFP; Gfap-CreERT2+/-;Nhe1f/f mice. Lastly, the role of Wnt/β-catenin pathway in resistance of Nhe1 Astro-KO mice to stroke-mediated BBB damage was tested by administration of Wnt/β-catenin inhibitor XAV-939. Taken together, we report that transforming reactive astrocyte function by upregulating astrocytic Wnt/β-catenin signaling activity is a novel mechanism to reduce the BBB endothelial damage, stimulate vascular repair, and restore cerebral blood flow after ischemic stroke.
2020-12-08 | GSE145839 | GEO
Project description:Ischemic stroke induces pathological glycogen deposition in astrocytes, but its role in post-injury neural dysfunction remains undefined. We reveal that glycogen-laden astrocytes in the ischemic penumbra undergo HDAC3-dependent mitochondrial fragmentation via a stress granule-mediated mechanism, exacerbating neuronal injury and hindering functional recovery. Mechanistic studies demonstrate that glycogen aggregates sequester cytoplasmic HDAC3, enabling its translocation to mitochondria. There, HDAC3 deacetylates outer mitochondrial membrane protein ATAD3A, promoting oligomerization-driven mitochondrial fission. Astrocyte-specific ATAD3A ablation prevents stroke-induced synaptic disorganization, neural circuit disruption, and cognitive deficits. Therapeutically, combined administration of cotadutide (a glycogen-depleting GLP-1/GCGR agonist) and HDAC3 inhibitor RGFP966 reverses glycogen accumulation, rescues mitochondrial architecture/function, and restores synaptic plasticity and circuit reorganization, thereby accelerating sensorimotor recovery. Our work identifies glycogen stress granules as pathogenic signaling hubs linking astrocytic metabolic stress to mitochondrial failure through compartmentalized HDAC3-ATAD3A crosstalk, and proposes a dual-target paradigm addressing both substrate overload and protein acetylation dynamics for stroke neurorestoration.
2025-05-10 | GSE295882 | GEO
Project description:Cluster analysis using nonlinear dimensionality reduction ([tSNE]) revealed the differences in global gene expression profiles of healthy and injured striatum, and identified clusters of cells with unique genetic signatures in both ischemic brain and hemorrhagic brain. Genes with p-value < 0.05 and fold change ≥1.5 were regarded as differentially expressed genes (DEGs). For astrocytes, 135 DEGs were downregulated in hemorrhagic stroke compared to ischemic stroke. The secondary profiling of astrocytic subtypes yielded 10 different subtypes with distinct functional cell identities. For microglia, tSNE map indicated the distribution and proportion of microglia/macrophage were very similar in in the ischemic and hemorrhagic stroke models. We obtained 75 DEGs in total (hemorrhagic stroke vs. ischemic stroke, 54 were upregulated, 21 were downregulated) .
2021-10-31 | GSE167593 | GEO
Project description:H2O2-induced astrocytic collagen triggers neuronal death in ischemic stroke [ATAC-seq]
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Project description:H2O2-induced astrocytic collagen triggers neuronal death in ischemic stroke [RNA-seq]
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