Single-nucleus RNA sequencing of human periventricular white matter in vascular dementia [scRNA-Seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1187214 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31370900.fastq.gz | Fastqsanger.gz | |||
| SRR31370889.fastq.gz | Fastqsanger.gz | |||
| SRR31370890.fastq.gz | Fastqsanger.gz | |||
| SRR31370891.fastq.gz | Fastqsanger.gz | |||
| SRR31370892.fastq.gz | Fastqsanger.gz |
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Project description:Single-nucleus RNA sequencing of human periventricular white matter comparing healthy age-matched controls with vascular dementia patients.
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Project description:Single-nucleus RNA sequencing of human periventricular white matter in vascular dementia [snRNA-Seq]
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Project description:Vascular dementia (VaD) refers to a variety of dementias driven by cerebrovascular disease and is the second leading cause of dementia globally. VaD may be caused by ischemic strokes, intracerebral hemorrhage, and/or cerebral small vessel disease, commonly identified as white matter hyperintensities on MRI. The mechanisms underlying these white matter lesions in the periventricular brain are poorly understood. In this study we perform an extensive transcriptomic analysis on human postmortem periventricular white matter lesions in patients with VaD with the goal of identifying molecular pathways in the disease. We find increased cellular stress responses in astrocytes, oligodendrocytes, and oligodendrocyte precursor cells as well as transcriptional and translational repression in microglia in our dataset. We show that several genes identified by GWAS as being associated with white matter disease are differentially expressed in cells in VaD. Finally, we compare our dataset to an independent snRNAseq dataset of PVWM in VaD and a scRNAseq dataset on human iPSC-derived microglia exposed to oxygen glucose deprivation (OGD). We identify the increase of the heat shock protein response as a conserved feature of VaD across celltypes and show that this increase is not linked to OGD exposure. Overall, our study is the first to show that increased heat shock protein responses are a common feature of lesioned PVWM in VaD and may represent a potential therapeutic target.
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Project description:Single-cell RNA sequencing of human iPSC-derived microglia (iMGL) exposed to normoxia, hypoxia or oxygen-glucose deprivation (OGD) for 24 hrs.
2024-12-06 | GSE282112 | GEO
Project description:Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia after Alzheimer’s disease (AD). Currently, the mechanistic insights into the evolution and progression of VCID remain elusive. White matter change represents an invariant feature. Compelling clinical neuroimaging and pathological evidence suggest a link between white matter changes and neurodegeneration. Our prior study detected hypoperfused lesions in mice with partial deficiency of endothelial nitric oxide (eNOS) at very young age, precisely matching to those hypoperfused areas identified in preclinical AD patients. White matter tracts are particularly susceptible to the vascular damage induced by chronic hypoperfusion. Using immunohistochemistry, we detected severe demyelination in the middle aged eNOS-deficient mice. The demyelinated areas were confined to cortical and subcortical areas including the corpus callosum and hippocampus. The intensity of demyelination correlated with behavioral deficits of gait and associative recognition memory performances. By Evans blue angiography, we detected blood-brain barrier (BBB) leakage as another early pathological change affecting frontal and parietal cortex in eNOS-deficient mic. Sodium nitrate fortified drinking water provided to young and middle aged eNOS-deficient mice completely prevented non-perfusion, BBB leakage, and white matter pathology, indicating that impaired endothelium-derived NO signaling may have caused these pathological events. Furthermore, genome-wide transcriptomic analysis revealed altered gene clusters most related to mitochondrial respiratory pathways selectively in the white matter of young eNOS-deficient mice. Using eNOS-deficient mice, we identified BBB breakdown and hypoperfusion as the two earliest pathological events, resulting from insufficient vascular NO signaling. We speculate that the compromised BBB and mild chronic hypoperfusion trigger vascular damage, along with oxidative stress and astrogliosis, accounting for the white matter pathological changes in the eNOS-deficient mouse model. We conclude that eNOS-deficient mice represent an ideal spontaneous evolving model for studying the earliest events leading to spontaneous white matter changes, which will be instrumental to future therapeutic testing of drug candidates and for targeting novel/specific vascular mechanisms contributing to VCID and AD.
2022-07-12 | GSE207693 | GEO
Project description:Survivors of myocardial infarction are at increased risk for vascular dementia. Neuroinflammation has been implicated in the pathogenesis of vascular dementia, yet little is known about the cellular and molecular mediators of neuroinflammation after myocardial infarction. Using a mouse model of myocardial infarction coupled with flow cytometric analyses and immunohistochemistry, we discovered increased monocyte abundance in the brain after myocardial infarction, which was associated with increases in brain-resident perivascular macrophages and microglia. Myeloid cell recruitment and activation was also observed in post-mortem brains of humans that died after myocardial infarction. Spatial and single cell transcriptomic profiling of brain-resident myeloid cells after experimental myocardial infarction revealed increased expression of monocyte chemoattractant proteins. In parallel, myocardial infarction increased crosstalk between brain-resident myeloid cells and oligodendrocytes, leading to neuroinflammation, white matter injury, and cognitive dysfunction. Inhibition of monocyte recruitment preserved white matter integrity and cognitive function, linking monocytes to neurodegeneration after myocardial infarction. Together, these preclinical and clinical results demonstrate that monocyte infiltration into the brain after myocardial infarction initiate neuropathological events that lead to vascular dementia.
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Project description:Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.
2020-05-20 | GSE131475 | GEO
Project description:Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. 16 Large White newborn female piglets were exposed to a tightly controlled hypoxic-ischemic insult using magnetic resonance spectroscopy (MRS) biomarkers. After hypoxia-ischemia (HI), piglets were randomized to: (i) no intervention (nâ=â8); (ii) RIPostC â with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (nâ=â8). Piglets in the remote post-conditioned group exhibited a reduction in white matter proton MRS lactate/N acetyl aspartate and increased whole brain phosphorus-31 MRS ATP over the 48âh after hypoxia-ischemia. Cell death (apoptosis) was reduced with RIPostC in the periventricular white matter, internal capsule and corpus callosum. There was also reduced microglial activation in corpus callosum and more surviving oligodendrocytes in corpus callosum and periventricular white matter. Our results demonstrate changes in the expression of 74 genes in the periventricular white matter 63 were down regulated and 11 were upregulated, that accompany the reductions in cell death and microglial activation seen following a remote post conditioning stimulus at a single 48h time point. (significance was calculated at p<0.05, one way ANOVA, Mann-Whitney unpaired, noe were found to be significant following a Benjamini-Hochberg FDR multipe testing correction). Many of these genes are thought to be important for the mediation of the neuroprotective effects of post-conditioning which suggests its genomic effects may persist for 48h. A full description of this work can be accessed at doi: 10.1177/0271678X15608862.
2016-09-21 | E-MTAB-5125 | biostudies-arrayexpress