Gene expression analysis after miR-125a-3p over-expression in oligodendrocyte precursor cells (OPCs)
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE143876 | GEO | 2021/01/21
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression analysis after miR-125a-3p over-expression in oligodendrocyte precursor cells (OPCs)
| PRJNA601955 | ENA
Project description:GPR17 silencing in OPCs accelerates their differentiation into fully mature oligodendrocytes. We performed a whole microarray profiling to identify altered signaling pathways after GPR17 silencing that are responsible for its effect on oligodendrocyte maturation.
2022-08-03 | GSE208409 | GEO
Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.
2018-02-22 | GSE110993 | GEO
Project description:Oligodendrocytes exist in a heterogenous state and are implicated in multiple neuropsychiatric diseases including dementia. Cortical oligodendrocytes are a glial population uniquely positioned to play a key role in neurodegeneration by synchronizing circuit connectivity but molecular pathways specific to this role are lacking. We utilized oligodendrocyte-specific translating ribosome affinity purification and RNA-seq (TRAP-seq) to transcriptionally profile adult mature oligodendrocytes from different regions of the central nervous system. Weighted gene co-expression network analysis (WGCNA) reveals distinct region-specific gene networks. Two of these mature myelinating oligodendrocyte gene networks uniquely define cortical oligodendrocytes and differentially regulate cortical myelination (M8) and synaptic signaling (M4). These two cortical oligodendrocyte gene networks are enriched for genes associated with dementia including MAPT and include multiple gene targets of the regulatory microRNA, miR-142-3p. Using a combination of TRAP-qPCR, miR-142-3p overexpression in vitro, and miR-142-null mice, we show that miR-142-3p negatively regulates cortical myelination. In rTg4510 tau-overexpressing mice, cortical myelination is compromised, and tau-mediated neurodegeneration is associated with gene co-expression networks that recapitulate both the M8 and M4 cortical oligodendrocyte gene networks identified from normal cortex. We further demonstrate overlapping gene networks in mature oligodendrocytes present in normal cortex, rTg4510 and miR-142-null mice, and existing datasets from human tauopathies to provide evidence for a critical role of miR-142-3p-regulated cortical myelination and oligodendrocyte-mediated synaptic signaling in neurodegeneration.
2023-04-04 | GSE211162 | GEO
Project description:Oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Chd7 is ATP-dependent chromatin-remodeling enzyme. We performed microarray analysis to examine changes in gene expression between control and Chd7 knockdown OPCs. Results provide insight into the function of Chd7 in oligodendrocyte development.
2018-03-01 | GSE95347 | GEO
Project description:The goal of the experiment is to determine the m6A tagged transcripts after the Mettl14 gene inactivation in OPCs and mature oligodendrocytes using Z score > 0 . Methods: mRNA from total RNA of Mettl14fl/fl OPCs and mature oligodendrocytes was purified with Dynabeads Oligo (dT)25 (ThermoFisher; 61006). The equivalent amount of input and m6A-imunoprecipitated RNA were prepared for library generation using the SMART-seq protocol as described (Picelli et al., 2014). Three biological replicates of control OPCs and three biological replicates of control oligodendrocytes were sequenced using Illumina NextSeq 500. Adapters were trimmed from original reads using Trimmomatic and low-quality reads were removed. The remaining reads were then mapped to the mouse genome (mm10) using STAR aligner (Dobin et al., 2013). To measure the relative m6A level per gene, the ratio of m6A IP/ Input was first calculated. The Z scores were then obtained by comparing the ratios (m6A IP/ Input) to the mean of the group to reflect the relative m6A level per gene on a transcriptome-wide scale. Results: The m6A-seq analyses detected 3554 m6A marked transcripts in OPCs and 2606 m6A marked transcripts in oligodendrocytes.There are 2806 transcripts with the m6A mark in OPCs that were present but not marked in oligodendrocytes , and 1626 transcripts that possessed the m6A mark in oligodendrocytes but not in OPCs . Only 23 of the shared transcripts , showed the m6A mark in both OPCs and oligodendrocytes. Conclusions: The dynamic nature of the m6A mark in oligodendrocyte lineage cells suggests that it may play an important role in oligodendrocyte differentiation and CNS myelination.
2019-12-31 | GSE124202 | GEO
Project description:In multiple sclerosis (MS) and experimental models of demyelination, myelin repair is mostly achieved by oligodendrocyte precursor cells (OPCs). To gain insight into the biological specificity of these adult precursors, in the perspective to better understand why remyelination often fails in MS, we performed a micro-array analysis on purified populations of murine OPCs and oligodendrocytes. We demonstrated that, in a control environment, M-bM-^@M-^\quiescentM-bM-^@M-^] adult OPCs are more mature than neonatal OPCs, with a mRNA profile closer to oligodendrocytes. However, when demyelination occurs, adult OPCs revert to an immature gene expression profile, acquiring higher migration and faster differentiation capacities. Among the many genes differentially regulated by these M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs, genes of the innate immune response, IL1M-NM-2 and CCL2 were strongly upregulated after demyelination, with increased protein expression in experimental demyelinating lesions and within MS plaques. We first showed in vitro that both IL1M-NM-2 and CCL2 M-bM-^@M-^\accountM-bM-^@M-^] for increased migration capacities of adult OPCs, an effect that is suppressed by corresponding receptor blockade. Focusing on Ccl2, we then demonstrated that lentiviral over-expression of Ccl2 increases motility of M-bM-^@M-^\quiescentM-bM-^@M-^] adult OPCs, which become as mobile as M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs. This in vitro gain of function was further confirmed in vivo, by showing an increased migration of grafted CG4 oligodendroglial cells over-expressing-Ccl2. These results, demonstrating that M-bM-^@M-^\activatedM-bM-^@M-^] adult OPCs upregulate immune cues favouring their migration, open new perspective of demyelination-induced immune-glial interactions, which might influence both oligodendroglial and inflammatory cells, therefore play a key role in lesion fate in multiple sclerosis. In this study, we loaded purified population of progenitors of oligodendrocytes (OPCs) (from neonatal, 2-month-old, 2-month-old and cuprizone-treated brains) and of mature oligodendrocytes (OLs) (2-month-old brains) and compared their gene expression. We compared gene expression of neonatal OPCs, adult OPCs, adult OLs and adult OPCs from control conditions and from demyelinating conditions, using 3 to 4 independant replicates in each group.
2014-11-06 | E-GEOD-48872 | biostudies-arrayexpress
Project description:Oligodendrocytes, the myelinating cells of the central nervous system, are essential for correct brain function. They originate from oligodendrocyte precursor cells (OPCs) through a differentiation process which is only incompletely understood and impaired in a variety of demyelinating diseases. Better knowledge of this differentiation holds the promise to develop novel therapies for these disorders. We investigated the differentiation of rat oligodendrocyte precursor cells to oligodendrocytes in vitro. After confirmation of differentiation by immunohistochemical analysis using cell type-specific marker proteins, we conducted a quantitative proteomics study using tandem mass tags (TMT). We investigated four time points of differentiation covering early, intermediate, and late stages. Data analysis was perfomed using Mascot and Maxquant.
2019-06-21 | PXD012544 | Pride
Project description:The age-related failure to regenerate lost oligodendrocytes from oligodendrocyte progenitor cells (OPCs) is associated with irreversible neurodegeneration in multiple sclerosis. Consequently, regenerative therapies for chronic demyelinating diseases remain a long sought after but elusive goal. Here we show that adult OPCs lose their inherent differentiation potential with increasing age. Moreover, aged OPCs do not remain responsive to pro-differentiation signals, posing significant constraints on the effectiveness of remyelination therapies based on the enhancement of OPC differentiation. We show that this reduced regenerative capacity is associated with hallmarks of cellular ageing, including reduced metabolic function and increased DNA damage. We find that fasting or treatment with metformin can reverse these changes and restore the regenerative capacity of aged OPCs, improving remyelination in aged animals following white matter injury. Importantly, aged OPCs treated with metformin regain their responsiveness to pro-differentiation factors, suggesting a potential for synergistic effects of rejuvenation and pro-differentiation therapies. Our findings have direct implications for understanding oligodendrocyte regeneration failure with ageing and how it might be reversed therapeutically.
2019-11-01 | GSE134765 | GEO
Project description:Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major unsolved problem. Consequently, predictive markers and a better understanding of resistance mechanisms are urgently needed. To investigate if the recently identified predictive miR-625-3p is functionally involved in oxPt resistance, stable and inducible models of miR-625-3p dysregulation were analyzed. Ectopic expression of miR-625-3p in CRC cells led to increased resistance towards oxPt. The mitogen-activated protein kinase (MAPK) kinase 6 (MAP2K6/MKK6) – an activator of p38 MAPK - was identified as a functional target of miR-625-3p, and, in agreement, was down-regulated in patients not responding to oxPt therapy. The miR-625-3p resistance phenotype could be reversed by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signaling as a possible driving force behind oxPt resistance. We conclude that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks.
2017-03-29 | MSV000080762 | MassIVE