Description:
<jats:title>Abstract</jats:title><jats:p>Despite the development of various in vitro differentiation protocols for the efficient derivation of specific cell types, human induced pluripotent stem cell (hiPSC) lines have varing ability to differentiate into specific lineages. Therefore, surrogate markers for accurately predicting the differentiation propensity of hiPSC lines may facilitate cell-based therapeutic product development and manufacture. We attempted to identify marker genes that could predict the differentiation propensity of hiPSCs into neural stem/progenitor cells (NS/PCs). Using Spearman’s rank correlation coefficients, we investigated genes in the undifferentiated state, the expression levels of which were significantly correlated with the neuronal differentiation propensity of several hiPSC lines. Among genes significantly correlated with NS/PC differentiation (<jats:italic>P</jats:italic> < 0.01), we identified <jats:italic>ROR2</jats:italic> as a novel predictive marker. <jats:italic>ROR2</jats:italic> expression in hiPSCs was negatively correlated with NS/PC differentiation tendency, regardless of the differentiation method, whereas its knockdown enhanced differentiation. <jats:italic>ROR2</jats:italic> regulates NS/PC differentiation, suggesting that <jats:italic>ROR2</jats:italic> is functionally essential for NS/PC differentiation. Selecting cell lines with relatively low <jats:italic>ROR2</jats:italic> expression facilitated identification of hiPSCs that can differentiate into NS/PCs. Cells with <jats:italic>ROR2</jats:italic> knockdown showed increased efficiency of differentiation into forebrain GABAergic neurons compared to controls. These findings suggest that <jats:italic>ROR2</jats:italic> is a surrogate marker for selecting hiPSC lines appropriate for NS/PC and GABAergic neuronal differentiations.</jats:p>