Gene expression profilings of neural progenitor cell derived from hiPSC with ROR2 knockdown

Human induced pluripotent stem cells (hiPSCs) have the ability to differentiate into a variety of cells and to self-renew in vitro. Because of these two characteristics, hiPSCs have been expected to provide new applications for regenerative medicine/cell therapy. Although various in vitro differentiation protocols have been developed for the efficient derivation of specific cell types, hiPSC lines vary in their ability to differentiate into specific lineages. Therefore, surrogate markers that accurately predict the differentiation propensity of hiPSC lines could be helpful for the development and manufacture of hiPSC-derived cells for therapies and in vitro assays. Here, we tried to identify the marker genes that potentially predicts the differentiation propensity of hiPSCs into neural progenitor cells (NPCs). Using ten hiPSC lines, we searched for genes significantly correlated between expression levels in the undifferentiated state and neuronal differentiation efficiency using two differentiation induction methods, and selected genes that were commonly and predominantly correlated with neuronal differentiation. Among the genes correlated with NPC differentiation, we identified ROR2 as a novel predictive marker of NPC differentiation. ROR2 expression in hiPSCs correlates negatively with NPC differentiation capacity, and ROR2 knockdown enhances NPC differentiation. These findings suggest that ROR2 serves as a useful surrogate marker for selecting hiPSC lines appropriate for NPC differentiation. To investigate how the ROR2 suppress differentiation of hiPSCs to NPC, we compared gene expression profiles during differentiation of hiPSC into late-stage NPC between ROR2 knockdown and control lines.