Single-cell and spatial transcriptomics analysis reveals that Pros1 oligodendrocytes are involved in endogenous neuroprotection after brainstem stroke

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106855 - 106855

Published: March 1, 2025

Brainstem stroke accounts only 7-10 % of all ischemic while it had more morbidity and mortality. As the predominant cellular component nerve tracts, oligodendrocytes might provide some neuroprotection against injury in context brainstem stroke, but underlying mechanism remains unclear. A mouse model was established, single-cell RNA sequencing spatial transcriptomic analysis were performed to elucidate phenotype within this context. Loss led neurological impairment following subsequent proliferation observed. We identified a subcluster Pros1+ oligodendrocytes, designated OLG8 cells. These cells increased number after enriched around peri-infarct zone. derived from oligodendrocyte progenitor cells, process found be regulated by Myo1e. that protected interneurons. Notably, overexpression Myo1e marked reduction infarct volume simultaneously improving recovery function. In conclusion, we novel cell subcluster, alleviated facilitating differentiation Our study provided insight into stroke.

Language: Английский

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Adhesion-Related Pathways and Functional Polarization of Astrocytes in Traumatic Brain Injury: Insights from Single-cell RNA Sequencing

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 27, 2025

Language: Английский

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Cross-Species Multi-Omics Analysis Reveals Myeloid-Driven Endothelial Oxidative Stress in Ischemic Stroke

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(4)

Published: April 16, 2025

Background: Ischemic stroke is a leading cause of mortality and disability worldwide, yet the interplay between peripheral central immune responses still only partially understood. Emerging evidence suggests that myeloid cells, when activated in periphery, infiltrate ischemic brain contribute to disruption blood-brain barrier (BBB) through both inflammatory metabolic mechanisms. Methods: In this study, we integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), spatial transcriptomics, flow cytometry data from human mouse models stroke. Mouse were induced by transient middle cerebral artery occlusion (tMCAO), tissues later collected at specified time points for analysis. We examined time-dependent transcriptional changes blood, delineated cell-type-specific profiling, validated infiltration into brain. also investigated endothelial reprogramming oxidative stress combining scMetabolism analyses (a computational R package inferring pathway activity level) with vitro oxygen-glucose deprivation/reperfusion (OGD/R) experiments. Results: Cross-species revealed modest early shift 3 h post-stroke, escalating significantly 24 h, robust myeloid-centric gene signatures conserved humans mice. Single-cell confirmed pronounced expansion neutrophils, monocytes, megakaryocytes coupled decrease T B lymphocytes. Spatial transcriptomics demonstrated substantial CD11b+ cells infarct core, which showed extensive interaction cells. Endothelial scRNA-seq reductions phosphorylation, glutathione, nicotinate pathways, together elevated pentose phosphate activity, suggestive compromised antioxidant capacity. Functional scoring further indicated diminished inflammation/repair potential, while OGD/R experiments morphological disruption, CD31 downregulation, increased 4-hydroxynonenal (4-HNE), underscoring importance damage BBB breakdown. Conclusions: These multi-omics findings highlight existence coordinated peripheral-central axis stroke, wherein cell recruitment vulnerability jointly exacerbate inflammation stress. The targeting injury myeloid-endothelial crosstalk may represent promising strategy mitigate secondary

Language: Английский

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Single-Cell RNA Sequencing of Brain Tissue Samples from Severe Traumatic Brain Injury Patients: A Protocol for Cellular Heterogeneity and Transcriptional Alteration Study

Indian Journal of Neurotrauma, Journal Year: 2025, Volume and Issue: unknown

Published: May 10, 2025

Abstract Severe traumatic brain injury (sTBI) leads to significant morbidity and mortality, often complicated by cerebral edema raised intracranial pressure (ICP). Understanding the molecular impact of these pathophysiological changes on injured adjacent noninjured is crucial for improving patient outcomes. Single-cell ribonucleic acid sequencing (scRNA-seq) offers a high-resolution approach studying cellular heterogeneity transcriptional alterations in TBI. This study aims utilize scRNA-seq analyze tissue patients with sTBI, identify differentially expressed genes, characterize response its relation ICP. A cross-sectional will be conducted, samples collected from sTBI patients. Tissue obtained during decompressive craniectomy, processed, analyzed using 10× Chromium system. Libraries sequenced Illumina NovaSeq 6000, transcriptomic data Seurat other bioinformatics tools. Bulk RNA performed validation. expected unique gene expression patterns associated edema, responses versus regions, provide insights into pathways contributing secondary injury. By leveraging scRNA-seq, this deeper understanding sTBI. The findings may aid discovering novel biomarkers therapeutic targets, ultimately clinical management strategies TBI

Language: Английский

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