Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA232749 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1066810_1.fastq.gz | Fastqsanger.gz | |||
| SRR1066810_2.fastq.gz | Fastqsanger.gz | |||
| SRR1066820.fastq.gz | Fastqsanger.gz | |||
| SRR1066811_1.fastq.gz | Fastqsanger.gz | |||
| SRR1066811_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
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Project description:The repair of white matter damage is of paramount importance for functional recovery after brain injuries.We report that interleukin-4 (IL-4) promotes oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 days after stroke. Consistent with these findings, intranasal delivery of IL-4 nanoparticles after stroke improved white matter integrity and attenuated long-term sensorimotor and cognitive deficits in wild-type mice, as revealed by histological immunostaining, electron microscopy, diffusion tensor imaging, and electrophysiology. The selective effect of IL-4 on remyelination was verified in an ex vivo organotypic model of demyelination. By leveraging primary oligodendrocyte progenitor cells (OPCs), microglia-depleted mice, and conditional OPC-specific PPARγ knockout mice, we discovered a direct salutary effect of IL-4 on oligodendrocyte differentiation that was mediated by the PPARγ axis. Our findings reveal a new regenerative role of IL-4 in the CNS, which lies beyond its known immunoregulatory functions on microglia/macrophages or peripheral lymphocytes. Therefore, intranasal IL-4 delivery may represent a novel therapeutic strategy to improve white matter integrity in stroke and other brain injuries.
2019-08-31 | GSE131774 | GEO
Project description:Tissue progenitors maintain the integrity of organ systems through aging and stress. The brain’s white matter regions experience ischemic lesions and age-dependent degeneration. Brain white matter contains progenitors, oligodendrocyte precursor cells (OPCs), which can repair some insults. The response of OPCs to white matter ischemia and aging is not known. We characterized the response of OPCs to white matter stroke using OPC reporter mice, cell migration tracking, OPC specific RNA sequencing, and mechanistic studies in candidate biochemical pathways in the aged brain. White matter stroke induces initial proliferation of local OPCs but blocks differentiation, shunting a portion into astrocytes. Candidate signaling pathways for this differentiation block including novel interactions of inhibin and matrilin-2 and new roles of NgR1 ligands following white matter stroke. Stroke induces inhibin expression in astrocytes and downregulates OPC matrilin-2 that contributes into OPC differentiation block. Antagonism of NgR1 ligands promotes OPC differentiation by attenuating the OPC astrocytic transformation and enhances functional recovery from stroke in aged animals.
2019-11-15 | GSE53737 | GEO
Project description:Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. In this study, we conducted single cell RNA-seq transcriptome analysis of corpus collosum and external capsule from wild-type (WT) and conditional Slc9a1 knockout (cKO) mice at 3 days post-stroke to study microglia-oligodendrocyte interactions.
2023-11-06 | GSE247102 | GEO
Project description:Cellular senescence is a form of adaptive cellular physiology associated with aging. Cellular senescence causes a pro-inflammatory cellular phenotype that impairs tissue regeneration, has been linked to stress, and is implicated in several human neurodegenerative diseases. We had previously determined that neural progenitor cells (NPCs) derived from primary progressive multiple sclerosis (PPMS) patient induced pluripotent stem (iPS) cell lines failed to promote oligodendrocyte progenitor cell (OPC) maturation whereas NPCs from age-matched control cell lines did so efficiently. Herein, we report that expression of hallmarks of cellular senescence were identified in SOX2+ progenitor cells within white matter lesions of human progressive MS autopsy brain tissues and PPMS patient iPS-derived NPCs. Expression of cellular senescence genes in PPMS NPCs was found to be reversible by treatment with rapamycin which then enhanced PPMS NPC support for oligodendrocyte differentiation. A proteomic analysis of the PPMS NPC secretome identified high mobility group box-1 (HMGB1), which was found to be a senescence-associated inhibitor of oligodendrocyte differentiation. Transcriptome analysis of OPCs revealed that senescent NPCs induced expression of epigenetic regulators mediated by extracellular HMGB1. Lastly, we determined that progenitor cells are a source of elevated HMGB1 in human white matter lesions. Based on these data, we conclude that cellular senescence contributes to altered progenitor cell functions in demyelinated lesions in MS. Moreover, these data implicate cellular aging and senescence as a process that contributes to remyelination failure in progressive MS which may impact how this disease is modeled and inform development of future myelin regeneration strategies.
2019-11-12 | PXD013060 | Pride
Project description:Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke
| PRJNA808986 | ENA
Project description:Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and under pathologic conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter. Here we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples, to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibers, and relate differences to the molecular profiles of these cells. For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibers was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.
2024-11-08 | GSE281006 | GEO
Project description:A hallmark of nervous system aging is a decline of white matter volume and function, but the underlying mechanisms leading to white matter pathology are unknown. Here, we found age-related alterations of oligodendrocytes with a reduction of total oligodendrocyte density in the aging murine white matter. Using single-cell RNA sequencing, we identify interferon-responsive oligodendrocytes, which localize in proximity of CD8+ T cells in the aging white matter. Absence of functional lymphocytes decreased oligodendrocyte reactivity and rescued oligodendrocyte loss, while T-cell checkpoint inhibition worsened the aging effect. In addition, we identified a subpopulation of immune cell dependent interferon-responsive microglia in the aging white matter, and co-culture experiments revealed that interferon- activated microglia triggered oligodendrocytes cell death. In summary, we provide evidence that T cells induced interferon-responsive oligodendrocytes and microglia are important modifiers of white matter aging.
2022-09-13 | GSE202579 | GEO
Project description:Adult neural progenitor cells (aNPCs) are a potential autologous cell source for cell replacement in neurologic diseases such as Parkinsonâs disease or stroke or for cell-based gene therapy for neurometabolic diseases. Easy accessibility, long-term expandability and detailed characterization of NPC properties are important requisites for their future translational/clinical applications. aNPC can be isolated from different regions of the adult human brain including the accessible subcortical white matter (aNPCWM), but systematic studies comparing long-term expanded aNPCWM with aNPC from neurogenic brain regions to check for their NPC characteristics and performance are not available. Freshly isolated cells from subcortical white matter and hippocampus (aNPCHIP) expressed oligodendrocyte progenitor cell (OPC) markers such as A2B5, NG2 and OLIG2 in ~20% of cells but no neural stem cell (NSC) markers such CD133 (Prominin1), NESTIN, SOX2 or PAX6. The EGF receptor (EGFR) protein was expressed in 18% of aNPCWM and 7% of aNPCHIP, but only a small fraction of 1 cell out 694 cells from white matter and only 1 out of 1,331 hippocampal cells were able to generate neurospheres. Studies comparing subcortical aNPCWM with their hippocampal counterparts showed that both NPC types expressed mainly markers of glial origin such as NG2, A2B5 and OLIG2, and the NSC/NPC marker Nestin, but no pericyte markers. Both NPC types were able to produce fully mature neurons, astrocytes and oligodendrocytes in comparable amounts to fetal NSC. Whole transcriptome analyses finally confirmed the strong similarity of aNPCWM with aNPCHIP. Our data show that aNPCWM are multipotent NPC with long-term expandability capacity similar to NPC from hippocampus making them an easily accessible source for possible autologous NPC-based treatment strategies. Isolation and propagation of multipotent NPCs. Adult human hippocampal (hip) and subcortical white matter (wm) tissue was obtained from routine epilepsy surgery procedures following informed consent of the subjects. All procedures were in accordance with the Helsinki convention and approved by the Ethical Committee of the University of Dresden (No. 47032006). All subjects underwent high-resolution magnetic resonance imaging excluding tumors and were screened for the presence of infectious disease. In all cases the neuropathological examinations did not reveal evidences for tumor formation. Gene expression Single-channel oligonucleotide microarray analysis. For the gene expression microarray analysis we used the Affimetrix U133A chips containing 22.215 probe sets representing at least 12.905 individual genes. The whole procedure was performed following the manufacturerâs standard protocol (Affimetrix, Santa Clara, CA). For the data processing, normalization was calculated with the GCRMA (GC content corrected Robust Multi-array Analysis) algorithm. fNSC: Human fetal neural stem cells, 2 biological rep aNPChip: Human adult neural progenitor cells isolated from hippocampus, 3 biological rep aNPCwm: Human adult neural progenitor cells isolated from white matter, 2 biological rep
2016-06-10 | E-GEOD-47921 | biostudies-arrayexpress
Project description:Hyperoxia is known to cause cerebral white matter injury in preterm infants with male sex being identified as an independent risk factor for poor neurodevelopmental outcome. We investigated the underlying mechanisms behind such a sex dependent difference by a comaparative protein profiling of male and female murine progenitor oligodendrocytes treated with 3 % or 80% oxygen. We demonstrate that following hyperoxia, the male derived oligodendrocyte progenitor cells (OPCs) are severely affected with respect to their energy metabolism, stress response and especially, maturation as compared to their female counterparts.
2021-09-08 | PXD011348 | Pride
Project description:Cerebral small vessel disease and brain white matter injury are worsened by cardiovascular risk factors including obesity. Molecular pathways in cerebral endothelial cells activated by chronic cerebrovascular risk factors alter cell-cell signaling, blocking endogenous and post-ischemic white matter repair. Using cell-specific translating ribosome affinity purification(RiboTag) in white matter endothelia and oligodendrocyte progenitor cells (OPCs), we identify a coordinated interleukin-chemokine signaling cascade within the oligovascular niche of subcortical white matter that is triggered by diet-induced obesity (DIO).DIO induces IL-17B signaling that acts on the cerebral endothelia through IL-17Rb to increase both circulating and local endothelial expression of CXCL5. In white matter endothelia, CXCL5 promotes the association of OPCs with the vasculature and triggers OPC gene expression programs regulating cell migration through chemokine signaling. Targeted blockade of IL-17B reduced vessel-associated OPCs by reducing endothelial CXCL5 expression. In multiple human cohorts, blood levels of CXCL5 function as a diagnostic and prognostic biomarker of vascular cognitive impairment.
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