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Differentiation of Oligodendrocyte Precursor Cells from Sox10-Venus Mice to Oligodendrocytes and Astrocytes.

ABSTRACT: Oligodendrocytes are well known as myelin-forming cells in the central nervous system (CNS). However, detailed mechanisms of oligodendrocyte differentiation and myelination are poorly understood, particularly due to the difficulty of the purification of murine oligodendrocyte precursor cells (OPCs). We have recently established a transgenic mouse line that expresses a fluorescent protein Venus under the promoter of Sox10, whose expression is restricted to OPCs and oligodendrocytes in the CNS. Here, we have characterized Venus-positive cells from the Sox10-Venus mouse brain for analyzing oligodendrocyte differentiation. We first purified Venus-positive cells from the postnatal day 0-2 brain by flow cytometry. Most of the Venus-positive cells expressed NG2, an OPC marker. After induction of differentiation, an increased population of galactocerebroside-positive oligodendrocytes and decrease of OPCs were observed in the Venus-positive culture. Furthermore, a time-lapse analysis showed that Venus-positive oligodendrocytes dynamically changed their morphology with highly branched cell processes during differentiation. In addition, we found that Venus-positive OPCs were able to differentiate to type II astrocytes. In vivo, OPCs and oligodendrocytes express Venus, and some of astrocytes were positive for Venus in the ventral cortex. Taken together, the Sox10-Venus mouse system is useful for analyzing differentiation and multipotency of murine OPCs.

SUBMITTER: Suzuki N

PROVIDER: S-EPMC5658394 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Differentiation of Oligodendrocyte Precursor Cells from Sox10-Venus Mice to Oligodendrocytes and Astrocytes.

Suzuki Nobuharu N Sekimoto Kaori K Hayashi Chikako C Mabuchi Yo Y Nakamura Tetsuya T Akazawa Chihiro C

Scientific reports 20171026 1

Oligodendrocytes are well known as myelin-forming cells in the central nervous system (CNS). However, detailed mechanisms of oligodendrocyte differentiation and myelination are poorly understood, particularly due to the difficulty of the purification of murine oligodendrocyte precursor cells (OPCs). We have recently established a transgenic mouse line that expresses a fluorescent protein Venus under the promoter of Sox10, whose expression is restricted to OPCs and oligodendrocytes in the CNS. He ...[more]

PMID: 29074959

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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.

Dataset Information

Differentiation of Oligodendrocyte Precursor Cells from Sox10-Venus Mice to Oligodendrocytes and Astrocytes.

Publications

Differentiation of Oligodendrocyte Precursor Cells from Sox10-Venus Mice to Oligodendrocytes and Astrocytes.

Similar Datasets

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