Induced neural stem cells-derived spinal cord progenitor cells as stable stage for rapid and efficient generation of human oligodendrocytes and motor neurons

Purpose: Previous studies have shown that oligodendrocytes and motor neurons have the same progenitors in the ventral spinal cord called spinal cord progenitor cells marked by oligodendrocyte lineage transcription factor 2 (Olig2). However, it is difficult to identify the spinal cord progenitor cell in vitro as they are present transiently and further transform into other neuronal (interneuron) and glial (oligodendrocyte) lineages during development. In the present study, we try to generated Olig2+ spinal cord progenitor cells from human induced neural stem cells (iNSCs) and identify those spinal cord progenitor cells in vitro Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were converted into induced neural stem cells (iNSCs), after they were identified by immunostaining using neural stem cell markers such as Nestin, Sox1, Sox2, iNSCs were transformed into Olig2+ spinal cord progenitor cells in 3 weeks by using small molecules. Results: Olig2+ spinal cord progenitor cells could expand for at least five passages and remained in a dividing state over a considerable period of time; in addition, the Olig2+ progenitor cells could mature into O4 and MBP positive oligodendrocytes and HB9 positive motor neurons in a short period. Conclusion: Our research provides a useful protocol for rapid generation of human oligodendrocytes and motor neurons from human iNSCs and demonstrates a progenitor cell model for exploring the origin of motor neurons and oligodendrocyte in vitro, which will contribute to research on the development of spinal cord and regenerative medicine.