Oligodendrocyte progenitor cells derived from mouse embryonic stem cells give rise to type-1 and type-2 astrocytes in vitro

Oligodendrocyte progenitor cells (OPCs) in primary culture can give rise to mature oligodendrocytes and type-2, but not type-1 astrocytes depending on the culture conditions. The OPCs thus are called oligodendrocyte-type-2 astrocyte (O2-A) progenitor cells. Mouse embryonic stem cells (mESCs) have been efficiently differentiated into OPCs; however, the fate plasticity of mESC-derived OPCs is not well characterized. In the present study, using GFP-Olig2 mESC line, we showed that the Olig2+/GFP+/A2B5+/NG2+ OPCs derived from GFP-Olig2 mESCs can mature into oligodendrocytes when co-cultured with mESC-derived neurons. Interestingly, when induced to astrocytic differentiation by bone morphogenetic protein-4, these mESC-derived OPCs can not only generate type-2 astrocytes, but also type-1 astrocytes. These results challenge the dogma that OPCs in culture can only generate type-2, but not type-1 astrocytes, and support the in vivo finding that during perinatal development, OPCs can give rise to a subset of type-1 astrocytes.

► We optimize our previous protocol for differentiating mESCs into OPCs. ► We establish the co-culture system of mESC-derived OPCs and neurons. ► The mESC-derived OPCs generate oligodendrocytes and astrocytes in co-culture. ► Induced by BMP4, mESC-derived OPCs generate both type-1 and type-2 astrocytes.