RNA-seq analysis for mRNA expression difference between male and female cultured oligodendrocyte precursor cells
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE135709 | GEO | 2021/08/01
REPOSITORIES: GEO
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Project description:Oligodendrocyte precursor cells (OPCs) regulate neuronal, glial and vascular systems in diverse ways and display phenotypic heterogeneity beyond their well-known role as a reservoir for mature oligodendrocytes. Here we demonstrated that perivascular OPCs in cerebral cortex were increased coupling with post-stroke angiogenesis in a mouse model of stroke induced by middle cerebral artery occlusion (MCAO). RNA-seq analysis revealed that primary cultured OPCs notably increased the gene expressions of numerous pro-angiogenic factors, while decreased those related to OPC maturation after oxygen glucose deprivation. The data showed that cerebral ischemia shifts the phenotype of OPCs to perivascular subtypes which can promote angiogenesis.
2020-05-12 | GSE114609 | 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:Following CNS demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. While remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis on OPCs isolated acutely from the brains of neonate, young and aged female rats. Approximately 60% of the proteins are expressed at different levels in OPCs from neonates compared to their adult counterparts. The amount of myelin-associated and cell adhesion proteins are increased with age, while cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC rodent proteome, revealing the distinct features of neonatal and adult OPCs, and providing new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.
2022-02-25 | PXD010383 | Pride
Project description:Following CNS demyelination, adult oligodendrocyte progenitor cells (OPCs) can differentiate into new myelin-forming oligodendrocytes in a regenerative process called remyelination. While remyelination is very efficient in young adults, its efficiency declines progressively with ageing. Here we performed proteomic analysis on OPCs isolated acutely from the brains of neonate, young and aged female rats. Approximately 60% of the proteins are expressed at different levels in OPCs from neonates compared to their adult counterparts. The amount of myelin-associated and cell adhesion proteins are increased with age, while cholesterol-biosynthesis, transcription factors and cell cycle proteins decreased. Our experiments provide the first ageing OPC rodent proteome, revealing the distinct features of neonatal and adult OPCs, and providing new insights into why remyelination efficiency declines with ageing and potential roles for aged OPCs in other neurodegenerative diseases.
2020-05-22 | PXD013708 | Pride
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:Oligodendrocyte progenitor cells (OPCs) are highly dynamic, abundant glial cells of the central nervous system (CNS) that are responsible for generating myelinating oligodendrocytes during development. OPCs are also mobilized to form new myelin sheaths in the adult CNS in response to environmental and behavioral changes, and play a crucial role in regenerating myelin following demyelination (remyelination). However, the rates of OPC proliferation and differentiation decline dramatically with aging, impairing homeostasis, remyelination, and potentially adaptive myelination during learning. To determine how aging influences OPCs, we generated a novel transgenic mouse line that expresses EGFP under the endogenous promoter/enhancer of Matrilin-4 (Matn4-mEGFP), allowing OPCs to be purified apart from perivascular and mural cells. OPCs isolated from the cerebral cortex of Matn4-mEGFP mice were subjected to single-cell RNA sequencing, providing enhanced resolution of transcriptional changes during key transitions from quiescence to proliferation and differentiation. Comparative analysis of OPCs isolated from mice aged 30 to 720 days, revealed that aging induces distinct inflammatory transcriptomic changes in OPCs in different states, including enhanced activation of HIF-1α and Wnt pathways. Inhibition of these pathways in acutely isolated OPCs from aged mice promoted their differentiation, suggesting that this enhanced signaling may contribute to the decreased regenerative potential of OPCs with aging. This Matn4-mEGFP mouse line and single-cell mRNA datasets of cortical OPCs across ages serve as a valuable reference to help define the molecular changes guiding their behavior in various physiological and pathological contexts.
2024-06-01 | GSE249268 | GEO
Project description:Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNg, IL1b and TNF we observed by RNA sequencing marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell-cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease.
2021-07-28 | GSE180604 | GEO
Project description:How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared to their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the events taking place between initial mutation and a fully developed tumor mass (pre-malignant phase) are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs, and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the pre-malignant phase, which revealed a dynamic multi-step transformation, starting with rapid but transient hyper-proliferative reactivation, followed by a long period of dormancy, then final malignant transformation. Using pharmacological approaches, we discovered that mTOR signaling is critical for both the initial OPC reactivation step and late stage tumor cell proliferation, and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs, and reveal an actionable multi-phasic reactivation process that turns slowly dividing OPCs into malignant gliomas. 44K Mouse Development Oligo Microarrays from Agilent Technologies were used for microarray analysis. For each experiment, total RNA was fluorescently labeled and hybridized directly against a common reference sample generated from the RNA pool of four WT P17 mouse brain neocortex.
2014-09-09 | E-GEOD-61282 | biostudies-arrayexpress
Project description:Astrocytes are instrumental in both maintaining CNS homeostasis and responding to tissue injury. While astrocyte activation may be a beneficial response to acute pathologies, prolonged reactive gliosis is thought to be injurious in neurodegenerative diseases, including multiple sclerosis (MS). A major limitation of studying neurodegenerative diseases is lack of human pathological specimens obtained during the acute stages, thereby relegating research to post mortem specimens often obtained years after the initiation of pathology. Rodent reactive astrocytes have been shown to be cytotoxic to neurons and oligodendrocytes but may differ from human cells, especially in diseases with known genetic susceptibility. Herein, we purified human CD49f+ astrocytes from differentiated induced pluripotent stem cells derived from individual patient and control peripheral white blood cell samples. We compared TNF and IL1a stimulated human reactive astrocytes from 7 persons with MS and 6 non-MS controls and show their specific astrocyte transcriptomic profiles are remarkably similar to those described in rodents. The functional effect of astrocyte conditioned media (ACM) was examined in a human oligodendrocyte precursor cell (OPC) line differentiation assay using a transgenic secreted reporter of myelin basic protein (MBP) expression. ACM was not cytotoxic to the OPCs but robustly inhibited the MBP reporter. No differences were seen between MS and control stimulated astrocytes at either the transcript level or in functional OPC suppression assays. We next used RNAseq to interrogate differentially expressed genes in the OPC lines that had suppressed differentiation from the human ACM. Remarkably, not only was OPC differentiation and myelin gene expression suppressed, but we observed induction of several immune pathways and Nf-κB signaling in OPCs exposed to the ACM. These data support the notion that reactive astrocytes can inhibit OPC differentiation thereby limiting their remyelination capacity, and that OPCs take on an immune profile in the context of inflammatory cues.
2022-02-14 | GSE196575 | GEO
Project description:The differentiation from neural stem cells (NSCs) to oligodendrocyte precursor cells (OPCs) is only incompletely understood. In the current study, we used the so-called neurosphere assay to study this process. We performed in vitro differentiation from neurospheres (which predominantly consist of NSCs) to oligospheres (consisting mainly of OPCs) and investigated their proteome by 6plex TMT-labeling and their phosphoproteome by 3plex dimethyl labeling. Among others, we identified a continuous upregulation of double cortin like kinase 1 (Dclk1) as well as its phosphorylation sites in the so-called SP-rich region. Using western blotting and qPCR, we show that two different Dclk1 isoforms (long and short) are present in NSCs and OPCs which gradually interchange during the investigated differentiation process. We further demonstrate that Dclk1 long is proteolytically processed into Dclk1 short and that this process is regulated via phosphorylation in the SP-rich region. Finally, we generated different BioID constructs fused to individual Dclk1 domains and investigate their interactome as well as potential substrates of Dclk1.
2023-08-18 | PXD040652 | Pride