Chromatin accessibility profiling of mouse microglia after ischemic stroke
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE319235 | GEO | 2026/03/11
REPOSITORIES: GEO
Similar Datasets
Project description:To investigate time-dependent changes in gene expression in microglia after ischemic stroke, we performed RNA-seq of FACS-sorted microglia from mouse brains at multiple time points after middle cerebral artery occlusion (MCAO).
2026-03-11 | GSE319237 | GEO
Project description:To investigate microglial heterogeneity and the effects of Zfp384 perturbation on brain cell populations after ischemic stroke, we performed single-cell RNA-seq of microglia and total brain cells from mouse brains at multiple conditions after middle cerebral artery occlusion (MCAO).
2026-03-11 | GSE319238 | GEO
Project description:To further delineate tPA functions in the blood, we examined the gene expression profiles induced by tPA in a rat model of ischemic stroke. Forty-two Sprague-Dawley rats were subjected to: 2 hours of middle cerebral artery occlusion (MCAO); a permanent-MCAO; or were used as controls. tPA was administered to half of the rats in each group at 3hours. Whole blood was drawn at 24 hours, and isolated RNA levels measured on Affymetrix Rat Genome 230 2.0 GeneChip microarrays to examine the entire RNA transcriptome. 42 samples, 7 groups in total ( 2 treatmented disease, 2 untreated disease, and 3 control groups), each group had 6 replicates
2014-03-29 | E-GEOD-21136 | biostudies-arrayexpress
Project description:Modulating M1/M2 polarization is a potential therapy for treating ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) held the capacity to regulate astrocytic polarization, but little is known about rTMS effects on microglia. Therefore, the present study aimed to investigate whether and how rTMS influence microglia polarization in ischemic stroke models. The 10-Hz rTMS was applied to transient middle cerebral artery occlusion (MCAO) rats and oxygen and glucose deprivation/ reoxygenation injured BV2 cells. Western blot, immunofluorescence and ELISA were used to detect M1/M2 markers. High-throughput sequencing, RT-PCR and FISH staining were adopted to test microRNA changes. The 10-Hz rTMS inhibited ischemia/reperfusion induced M1 microglia and significantly increased let-7b-5p. HMGA2 was proved to be the target protein of let-7b-5p and its downstream NF-κB signaling pathway were inhibited by rTMS. Microglia culture medium (MCM) collected from rTMS treated microglia had low TNF-α but high IL-10 concentration, leading to reduced neural death, minor ischemic volumes and improved functional recovery of MCAO animals. However, knockdown of let-7b-5p by antagomir reversed rTMS effects on microglia. In conclusion, high-frequency rTMS could improve functional recovery through inhibiting M1 microglia polarization via regulating let-7b-5p/HMGA2/NF-κB signaling pathway in cerebral ischemic stroke models.
2022-08-10 | GSE192910 | GEO
Project description:Ischemic stroke is a common acute CNS disorder leading to nearly half a million deaths per year in Europe. The high mortality is primarily owed to the limited treatment options of restoring blood flow in a narrow time window of several hours. Furthermore, inflammatory processes in the days and weeks after ischemic stroke contribute to tissue loss and neurological deficits. The key cells that influence and control this inflammatory cascade are microglia, the innate immune cells of the CNS. Microglia can be influenced and activated by e.g. lipopolysaccharide (LPS),a bacterial cell membrane component. It has been previously shown, that repetitive LPS stimuli prior to infarction (termed immunological preconditioning) lead to reduced infarct volumina in mouse models of ischemic stroke. Furthermore, our laboratory has shown, that phosphoinositide-3 kinase gamma mediates microglial functions after LPS-preconditioning. Hence, the aim of this work was to characterize proteomic alterations in microglia with (I) ischemic stroke in general in the tMCAO (transient middle cerebral artery occlusion) mouse model of ischemic stroke, (II) the influence of LPS-preconditioning on microglial proteomic alterations after tMCAO and (III) the role of PI3Ky in the microglial proteomic changes after tMCAO and preconditioning. This was done by a single LPS injection 3 days before tMCAO in wildtype mice and mice with PI3Ky knockout or knockin of the kinase dead form of PI3Ky.
2024-03-22 | PXD031930 | Pride
Project description:To further delineate tPA functions in the blood, we examined the gene expression profiles induced by tPA in a rat model of ischemic stroke. Forty-two Sprague-Dawley rats were subjected to: 2 hours of middle cerebral artery occlusion (MCAO); a permanent-MCAO; or were used as controls. tPA was administered to half of the rats in each group at 3hours. Whole blood was drawn at 24 hours, and isolated RNA levels measured on Affymetrix Rat Genome 230 2.0 GeneChip microarrays to examine the entire RNA transcriptome.
2014-03-29 | GSE21136 | GEO
Project description:Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners.
2018-07-11 | GSE116878 | GEO
Project description:To detect chromatin loops maintaining genomic interactions among enhancer and promoter regions in microglia after ischemic stroke, we performed H3K27ac HiChIP of FACS-sorted CD45intCD11bint microglia from sham-operated and post-ischemic day 6 mouse brains.
2026-03-11 | GSE319240 | GEO
Project description:In the acute phase of ischemic stroke, endothelial cell (EC) dysfunction leads to breakdown of the blood-brain barrier with increased vascular permeability, vascular inflammation, and transendothelial migration of leukocytes. ECs are also critical for long-term regenerative processes, such as post-stroke angiogenesis, enabling the transition from brain injury to repair. Yes-associated protein 1 (YAP) and WW domain-containing transcriptional regulator 1 (TAZ) are co-transcriptional regulators of EC proliferation and apoptosis. Several studies showed that YAP/TAZ is essential for developmental angiogenesis. However, the role of YAP/TAZ in adult angiogenesis and particularly in experimental stroke is unknown. Here, we subjected mice with an inducible EC-specific deletion of YAP and TAZ (YT-iKO) to 30-min middle cerebral artery occlusion (MCAo) followed by reperfusion to investigate the effects of endothelial YAP/TAZ on acute and long-term outcome after ischemic stroke. First, we examined mRNA expression of genes related to YAP/TAZ signaling in ischemic brain tissue, such as Id1, Smad6, Ankrd and Ccn2. We found a transient induction with highest expression levels acutely after stroke. Surprisingly, endothelial YAP/TAZ deficiency resulted in reduced lesion volumes 28 days after MCAo, whereas acute lesion size 3 days after stroke did not differ. Moreover, Yap/Taz iEC-KO animals showed no gross differences in vessels morphology 28 days after stroke, and no effect was detected on blood vessel density and EC density. We therefore speculated whether angiogenesis-independent effects of YAP/TAZ might also be associated with improved long-term outcome after stroke. To better understand the underlying mechanisms, we performed RNA sequencing of ECs isolated from ischemic brain tissue of YT-iKO compared with CTRL animals 72h post stroke. Here, we identified differently expressed gene sets involved in inflammatory responses. Therefore, we studied the non-endothelial tissue environment of the brain. We found, that EC YAP/TAZ deletion led to increased expression of anti-inflammatory genes accompanied by increased infiltration of myeloid cells, suggesting a protective phenotype. Besides, acute microglia proliferation was reduced in Y/T-iKO animals. Overall, our results provide new insights into the role of endothelial YAP/TAZ in neuroinflammation after cerebral ischemia. YAP/TAZ may therefore be a potential therapeutic target for the treatment of ischemic stroke.
2025-12-04 | GSE265949 | GEO
Project description:The rapid accumulation of self-renewed polarized microglia in the penumbra is the critical neuroinflammatory process after the onset of ischemic stroke, leading to secondary demyelination and neuronal loss. HDAC3 has been reported to regulate cell proliferation of tumour cells and modulate neuroinflammation. However, the mechanism by which HDAC3 regulates microgliosis and microglial polarization remains ambiguous. Herein, we demonstrated that microglia-specific ablation of HDAC3 (HDAC3-miKO) ameliorated poststroke long-term functional and histological outcomes. Starting with unbiased RNA seq of microglia, we identified mitosis as the most significant process reversed by loss of HDAC3. Notably, HDAC3-miKO specifically inhibited the proliferation of M1-like microglia but not M2-like microglia, resulting in microglial transition to an M1-like state. Moreover, ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) revealed that HDAC3 deletion induced drastic closing of accessible regions enriched with motifs for PU.1. Taken together, we uncovered for the first time that HDAC3/PU.1-mediated differential proliferation-related reprogramming in different microglia populations drives poststroke inflammatory state transition of microglia and thereby contributes to the pathophysiology of ischemic stroke.
2024-03-13 | GSE220041 | GEO