Abstract
Emerging evidence indicates that epidermal growth factor (EGF) signaling plays a positive role in myelin development and repair, but little is known about its biological effects on the early generation and differentiation of oligodendrocyte (OL) lineage cells. In this study, we investigated the role of EGF in early OL development with isolated glial restricted precursor (GRP) cells. It was found that EGF collaborated with Platelet Derived Growth Factor-AA (PDGFaa) to promote the survival and self-renewal of GRP cells, but predisposed GRP cells to develop into O4− early-stage oligodendrocyte precursor cells (OPCs) in the absence of or PDGFaa. In OPCs, EGF synergized with PDGFaa to maintain their O4 negative antigenic phenotype. Upon PDGFaa withdrawal, EGF promoted the terminal differentiation of OPCs by reducing apoptosis and increasing the number of mature OLs. Together, these data revealed that EGF is an important mitogen to enhance oligodendroglial development.
Highlights
Oligodendrocytes (OLs) elaborate insulating myelin sheaths that wrap around axons to ensure the rapid conduction of nerve impulses and axonal survival (Qiu, 2013; Zhang et al, 2013; Blank and Prinz, 2014; Alizadeh et al, 2015; Rao and Pearse, 2016)
Immunopurified A2B5+ cells from E13.5 spinal tissues were adjusted to a cell density of 10 cells/ml with glial basal medium supplemented with 10 ng/ml epidermal growth factor (EGF) and Platelet Derived Growth Factor-AA (PDGFaa), the cell suspension was added into fibronectin/laminin-coated 96-well plates at 100 μl/well, and wells with a single cell were marked for further culture
Immunopurified glial restricted precursor (GRP) cells from E13.5 spinal tissues were adjusted to a cell density of 10 cells/ml with glial basal medium supplemented, the cell suspension was added into fibronectin/laminin-coated 48-well plates at 100 μl/well in the presence of EGF and PDGFaa (10 ng/ml) for 24 h before being exposed to the factors as indicated in the "Results" Section wells with a single cell were marked for further culture
Summary
Oligodendrocytes (OLs) elaborate insulating myelin sheaths that wrap around axons to ensure the rapid conduction of nerve impulses and axonal survival (Qiu, 2013; Zhang et al, 2013; Blank and Prinz, 2014; Alizadeh et al, 2015; Rao and Pearse, 2016). Tripotential GRP cells generate bipotential oligodendrocyte precursor cells (OPCs) which are capable of differentiating into either OLs or type II astrocytes (Morath and Mayer-Pröschel, 2001; Gregori et al, 2002). OPCs proliferate and migrate throughout the CNS during late mouse embryonic development, and later differentiate into mature myelinating OLs (Fernandez et al, 2004; Cai et al, 2010; Chen et al, 2015).
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