Schwann cells demonstrated lineage plasticity in culture and acquired oligodendrocyte phenotypes

Abstract

Schwann cells and oligodendrocytes are myelin-forming glial cells found in the peripheral and central nervous systems, respectively. Despite being similar in function, the two cell types have distinct developmental origins. In cultured Schwann cells, however, we serendipitously observed expression of the oligodendrocyte lineage fate determining factor Olig2. Purified Schwann cell cultures were prepared from neonatal rat sciatic nerves. Olig2-positive Schwann cells (OL2-SCs) were detected at 25-30 DIV. By 50-60 DIV, OL2-SCs acquired polydendritic morphology typical of oligodendrocyte precursors. This was accompanied by a decline in Schwann cell marker expression. The OP-like cells were termed Schwann cell-derived oligodendrocyte precursors (SC-OPs). We therefore hypothesized that the peripheral nervous system environment is essential for the maintenance of Schwann cell identity. Co-culture of OL2-SCs with dorsal root ganglia neurons prevented conversion in SC-OPs. In contrast, SC-OPs co-cultured with dorsal root ganglia neurons continued differentiation into mature oligodendrocyte-like cells with myelin basic protein-positive segments along multiple axons. Transplantation of SC-Ops into the brain of myelin deficient Shiverer mice resulted in the generation of myelin-forming oligodendrocytes. Our results revealed 'lineage switching' capability of Schwann cells isolated from the peripheral nervous system. Preservation of Schwann cell identity in vitro requires signalling cues derived from peripheral neurons.