Zinc Promotes Patient-Derived Induced Pluripotent Stem Cell Neural Differentiation via ERK-STAT Signaling

Abstract

Nerve regeneration remains a challenge. Patient-derived induced pluripotent stem cell(iPSC) differentiated neural stem cells (iNSCs) provide a promising hope. Zinc is closely involved in central nervous system (CNS) development and metabolism, but its role on iPSCs neural differentiation is elusive because of and lacking zinc detection methods of zinc in live cells are limited. In this study, intracellular zinc was detected in real-time by a novel zinc fluorescent chemosensor (ZFC), whose advantages are real-time detection and limited damage to cells; and intracellular zinc was shown to be increased during the iPSC neural induction process. iPSC neural Neural differentiation was promoted with the addition of zinc chloride (ZnCl2), but and inhibited with the addition of zinc chelator N,N,N0,N0-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN) indicated by western blot and ELISA analysis of neural stem cell marker Nestin expression, and measurement of neurite-like structures. Meanwhile, Mechanistically, the phosphorylation level of ERK1/2 and STAT3 was also regulated by changed with the zinc level, suggesting that zinc may affect the neural differentiation of iPSCs through ERK-STAT signaling. In conclusion, our study shows the important role of zinc in iPSC neural differentiation and suggests a new idea for iPSC-derived NSC application in nerve regeneration.