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Oligodendrocyte progenitor cells become regionally diverse and heterogeneous with age

ABSTRACT: Oligodendrocyte progenitor cells become regionally diverse and heterogeneous with age

PROVIDER: PRJNA495612 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7993830.fastq.gz	Fastqsanger.gz
	SRR7993840.fastq.gz	Fastqsanger.gz
	SRR7993831.fastq.gz	Fastqsanger.gz
	SRR7993841.fastq.gz	Fastqsanger.gz
	SRR7993832.fastq.gz	Fastqsanger.gz

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Oligodendrocyte progenitor cells become regionally diverse and heterogeneous with age

Project description:Oligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during central nervous system (CNS) development, are the main proliferative cells in the adult brain. OPCs are conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell electrophysiological recordings, that OPCs start out as a homogeneous population, but become functionally heterogeneous, varying both within and between brain regions and with age. These electrophysiological changes in OPCs correlate with the differentiation potential of OPCs; thus, they may underlie the differentiational differences in OPCs between regions and likewise differentiation failure with age.

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Project description:Stem cell biology has garnered much attention due to its potential to impact human health through disease modeling and cell replacement therapy. This is especially pertinent to myelin-related disorders such as multiple sclerosis and leukodystrophies where restoration of normal oligodendrocyte function could provide an effective treatment. Progress in myelin repair has been constrained by the difficulty in generating pure populations of oligodendrocyte progenitor cells (OPCs) in sufficient quantities. Pluripotent stem cells theoretically provide an unlimited source of OPCs but significant advances are currently hindered by heterogeneous differentiation strategies that lack reproducibility. Here we provide a platform for the directed differentiation of pluripotent mouse epiblast stem cells (EpiSCs) through a defined series of developmental transitions into a pure population of highly expandable OPCs in ten days. These OPCs robustly differentiate into myelinating oligodendrocytes both in vitro and in vivo. Our results demonstrate that pluripotent stem cells can provide a pure population of clinically-relevant, myelinogenic oligodendrocytes and offer a tractable platform for defining the molecular regulation of oligodendrocyte development, drug screening, and potential cell-based remyelinating therapies. 6 total samples were analyzed. Pluripotent epiblast stem cells (EpiSCs) were differentiated to patterned neural rosettes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes. OPCs and oligodedrocytes were analyzed at two separate passages (3 and 11).

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