Summary Sox2 is a key player in the maintenance of pluripotency and stemness, and thus inhibition of its function would abrogate the stemness of pluripotent cells and induce differentiation into several types of cells. Herein we describe a strategy that relies on a combination of Sox2 inhibition with lineage-specific induction to promote efficient and selective differentiation of pluripotent P19 cells into neurons. When P19 cells transduced with Skp protein, an inhibitor of Sox2, are incubated with a neurogenesis inducer, the cells are selectively converted into neurons that generate depolarization-induced sodium currents and action potentials. This finding indicates that the differentiated neurons are electrophysiologically active. Signaling pathway studies lead us to conclude that a combination of Skp with the neurogenesis inducer enhances neurogenesis in P19 cells by activating Wnt and Notch pathways. The present differentiation protocol could be valuable to selectively generate functionally active neurons from pluripotent cells.
Bibliographical noteFunding Information:
This study was supported by grants from the National Creative Research Initiative (I.S., 2010–0018272 ) program, the National Research Foundation ( NRF-2014R1A2A2A01006940 and NRF-2014M3A7B4051596.940 to E.C. and NRF-2012M3A9C6049939 to K.K.K.), and The next-Generation BioGreen 21 Program (K.K.K., SSAC PJ01107005 ).
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Drug Discovery
- Clinical Biochemistry