Differential Gene Expression in Oligodendrocyte Progenitor Cells, Oligodendrocytes and Type II Astrocytes

Abstract

Oligodendrocyte precursor cells (OPCs) are bipotential progenitor cells that can differentiate into myelin-forming oligodendrocytes or functionally undetermined type II astrocytes. Transplantation of OPCs is an attractive therapy for demyelinating diseases. However, due to their bipotential differentiation potential, the majority of OPCs differentiate into astrocytes at transplanted sites. It is therefore important to understand the molecular mechanisms that regulate the transition from OPCs to oligodendrocytes or astrocytes. In this study, we isolated OPCs from the spinal cords of rat embryos (16 days old) and induced them to differentiate into oligodendrocytes or type II astrocytes in the absence or presence of 10% fetal bovine serum, respectively. RNAs were extracted from each cell population and hybridized to GeneChip with 28,700 rat genes. Using the criterion of fold change > 4 in the expression level, we identified 83 genes that were up-regulated and 89 genes that were down-regulated in oligodendrocytes, and 92 genes that were up-regulated and 86 that were down-regulated in type II astrocytes compared with OPCs. The up-regulated genes, such as activating transcription factor 3 and myelin basic protein in oligodendrocytes or claudin 11 in type II astrocytes, might contribute to OPC differentiation and represent constitutive components of oligodendrocytes or type II astrocytes. The down-regulated genes in both oligodendrocytes and type II astrocytes, such as transcription factor 19, might be involved in maintaining self-renewal and/or represent the property of OPCs. These results provide new insights into the elucidation of the molecular mechanisms, by which OPCs differentiate to oligodendrocytes or type II astrocytes.

Reprogramming of mouse embryonic fibroblasts into induced oligodendrocyte progenitor cells via nanovector-mediated indirect lineage conversion

“…We also confirmed that 10 % FBS could contribute to converting OPCs into type Ⅱ astrocytes in vitro. Therefore, primary OPCs isolated with our modified isolation and purification strategies had bidirectional differentiation potentials, these results were in accordance with that reported by Hu et al (2011) [37], which laid the foundation for higher-efficiently harvesting OPCs for cell replacement therapy, disease modeling, and so on.…”

Erythropoietin Increases Myelination in Oligodendrocytes: Gene Expression Profiling Reveals Early Induction of Genes Involved in Lipid Transport and Metabolism

“…These include three of the genes identified by DAVID in the functional groups “nervous system differentiation” and “cell adhesion” ( Cdhr2, Mag, Ntm ). In addition, Mag and Pnlip were reported as upregulated in primary rat OL compared with OPC ( 20 , 34 , 36 , 45 ).…”

High-Content Phenotypic Screening and Triaging Strategy to Identify Small Molecules Driving Oligodendrocyte Progenitor Cell Differentiation

“…Compounds identified through this effort have the potential to stimulate endogenous OPCs to differentiate and remyelinate demyelinated axons, thereby contributing new modalities of treatment for neurodegenerative diseases such as MS. A small-molecule approach to achieve this objective has a higher chance of resulting in an orally bioavailable therapy that is able to cross the blood-brain barrier and reach the CNS, compared to biological agents. Although significant data exist regarding the pathways and gene expression modifications during OPC differentiation, 5,[15][16][17][18][19] in the context of developing therapeutics there are important considerations concerning the specificity of putative targets. Therefore, we chose the approach of a phenotypic assay to identify compounds competent to initiate differentiation of both rat CG-4 cells and primary OPCs but not of the MSC-derived rodent progenitor cell (C2C12) in a comparable assay format (similar time and stimulus).…”