RRC ID 77861
著者 Kuroda T, Yasuda S, Matsuyama S, Miura T, Sawada R, Matsuyama A, Yamamoto Y, Morioka MS, Kawaji H, Kasukawa T, Itoh M, Akutsu H, Kawai J, Sato Y.
タイトル ROR2 expression predicts human induced pluripotent stem cell differentiation into neural stem/progenitor cells and GABAergic neurons.
ジャーナル Sci Rep
Abstract 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 (P < 0.01), we identified ROR2 as a novel predictive marker. ROR2 expression in hiPSCs was negatively correlated with NS/PC differentiation tendency, regardless of the differentiation method, whereas its knockdown enhanced differentiation. ROR2 regulates NS/PC differentiation, suggesting that ROR2 is functionally essential for NS/PC differentiation. Selecting cell lines with relatively low ROR2 expression facilitated identification of hiPSCs that can differentiate into NS/PCs. Cells with ROR2 knockdown showed increased efficiency of differentiation into forebrain GABAergic neurons compared to controls. These findings suggest that ROR2 is a surrogate marker for selecting hiPSC lines appropriate for NS/PC and GABAergic neuronal differentiations.
巻・号 14(1)
ページ 690
公開日 2024-1-6
DOI 10.1038/s41598-023-51082-4
PII 10.1038/s41598-023-51082-4
PMID 38184695
PMC PMC10771438
MeSH Cell Differentiation / genetics Cell Line Commerce GABAergic Neurons Humans Induced Pluripotent Stem Cells* Receptor Tyrosine Kinase-like Orphan Receptors / genetics
IF 3.998
リソース情報
ヒト・動物細胞 201B7(HPS0063) 253G1(HPS0002) 409B2(HPS0076) HiPS-RIKEN-1A(HPS0003) HiPS-RIKEN-2A(HPS0009) HiPS-RIKEN-12A(HPS0029)