CD140a identifies a population of highly myelinogenic, migration-competent, and efficiently engrafting human oligodendrocyte progenitor cells

Experimental models of myelin disorders can be treated by the transplantation of oligodendrocyte progenitor cells (OPCs) into the affected brain or spinal cord. OPCs express gangliosides recognized by MAb A2B5, but this marker also identifies lineage-restricted astrocytes and immature neurons. To establish a more efficient means of isolating myelinogenic OPCs, we asked if FACS could be used to sort PDGFα receptor+ cells from fetal human forebrain, based on expression of the PDGFRα epitope CD140a. CD140a+ isolates were maintained as mitotic bipotential progenitors that could be instructed to either oligodendrocyte or astrocyte fate. Transplanted CD140a+ cells were highly migratory, and rapidly and robustly myelinated the hypomyelinated shiverer mouse brain, more efficiently than did A2B5-sorted cells. Microarray analysis of CD140a+ cells revealed their differential expression of CD9, as well as of PTN-PTPRZ1, wnt, notch and BMP pathway components, indicating the dynamic interaction of self-renewal and fate-restricting pathways in these cells.