Expression pattern of transcription factor SOX2 in reprogrammed oligodendrocyte precursor cells and microglias: Implications for glial neurogenesis.

Abstract

Oligodendrocyte Precursor Cells (OPCs) can revert to multipotential Neural Stem-Like Cells (NSLCs) which can self-renew and give rise to neurons, astrocytes and oligodendrocytes when exposed to certain extracellular signals. This is a significant progress to understand developmental neurobiology, in particularly the possibility of converting glia to stem cells for the treatment of neurological disorders. Similarly, recent findings revealed that brain-resident microglias (MGs) can be converted to multipotential state through de-differentiation. In this study, we investigated the role of SRY (sex-determining region)-box 2 (SOX2), a high-mobility group DNA binding domain transcription factor, in the reprogramming of OPCs and MGs and molecular pathways involved in these process. Immunocytochemical analyses demonstrated that expression of SOX2 was upregulated in the reprogrammed MGs and OPCs as well as other neural stem cell markers such as CD15 and nestin. Western blot and double immunostaining analyses further confirmed that activation of bone morphogenetic proteins (BMPs) signaling partnering with SOX2 might be one of the molecular pathways involved in lineage reprogramming of OPCs which is also true in the reversion of MGs. Taken together, these results indicated that lineage reprogramming of OPCs and MGs are both controlled by the same signaling pathway and glia can be reprogrammed in culture by inducing expression of neurogenic transcription factors to transgress their lineage restriction and can stably acquire a neuronal identity. Our results suggested innovative perspectives for cell therapy with glia cells.