Differentiation of Human Induced Pluripotent Stem Cells to OLIG2 Positive Ventral Neural Tube Progenitors

Abstract

Established protocols to generate OPCs from pluripotent stem cells still have several critical drawbacks including being cumbersome, time consuming, and incompatible for autologous stem cell therapies, that have impeded the translation of stem cell derived OPCs in cell transplantation therapies. The 3D culture system employed in these protocols introduces many undefined variables modulating growth factor response by cells. These include variability in culture environment among cells in a batch, differences in cell number and cell density batch to batch, and site to site variations, all of which impact the identity, number and purity of the cells being generated. By constraining to a 2D monolayer system and systematically experimenting with the growth factors and inhibitors currently used to induce OPC differentiation, a shorter, adherent protocol for generating iPSC-derived OLIG2+ ventral neural tube progenitors via an intermediate neuromesodermal progenitor has been developed in the Dutton laboratory.