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Transcriptional profiling of murine oligodendrocyte precursor cells across the lifespan

ABSTRACT: Transcriptional profiling of murine oligodendrocyte precursor cells across the lifespan

PROVIDER: PRJNA1048408 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27044604.fastq.gz	Fastqsanger.gz
	SRR27044605.fastq.gz	Fastqsanger.gz
	SRR27044606.fastq.gz	Fastqsanger.gz
	SRR27044607.fastq.gz	Fastqsanger.gz
	SRR27044608.fastq.gz	Fastqsanger.gz

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Transcriptional profiling of murine oligodendrocyte precursor cells across the lifespan

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.

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Investigation of Oligodendrocyte Precursor Cell Differentiation by Quantitative Proteomics

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.

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Project description:Glial cytoplasmic inclusion is the pathological hallmark of multiple system atrophy commonly observed as alpha-synulcien-positive aggregates within oligodendrocytes. We elucidated that preformed alpha-synulcien fibrils triggers multimerization and upsurge of endogenous alpha-synulcien in oligodendrocyte precursor cells which is attributable to insufficient autophagic proteolysis. To assess the functional influence of alpha-synuclein fibrils application on oligodendrocyte precursor cells, RNA-seq analysis was performed. The data revealed that alpha-synulcien fibrils interfered with numerous protein expressions associated with neuronal support and myelination.

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