Nerve regeneration remains a challenge. Patient-derived induced pluripotent stem cell (iPSC)-differentiated neural stem cells (NSCs) provide a promising hope. Zinc is closely involved in central nervous system development and metabolism, but its role on iPSC neural differentiation is elusive and zinc detection methods in live cells are limited. In this study, intracellular zinc was detected in real time by a zinc fluorescent chemosensor and was shown to be increased during the iPSC neural induction process. iPSC neural differentiation was promoted with the addition of zinc chloride (ZnCl₂) and inhibited with the addition of zinc chelator N,N,N0,N0-tetrakis(2-pyridylmethyl)-ethylenediamine, indicated by western blot and enzyme-linked immunosorbent assay analysis of NSC marker Nestin expression and measurement of neurite-like structures. Mechanistically, the phosphorylation level of ERK1/2 and STAT3 was 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.

中文翻译：

---

锌通过ERK-STAT信号促进患者诱导的多能干细胞神经分化。

神经再生仍然是一个挑战。患者来源的诱导多能干细胞（iPSC）分化的神经干细胞（NSC）提供了有希望的希望。锌与中枢神经系统的发育和代谢密切相关，但其在iPSC神经分化中的作用却难以捉摸，并且活细胞中的锌检测方法受到限制。在这项研究中，锌荧光化学传感器实时检测到细胞内锌，并显示在iPSC神经诱导过程中细胞内锌会增加。氯化锌（ZnCl ₂）促进iPSC神经分化，锌螯合剂N，N，N 0，N抑制iPSC神经分化。0-四（2-吡啶基甲基）-乙二胺，通过Western印迹和NSC标记Nestin表达的酶联免疫吸附分析和神经突样结构的测定表明。从机制上讲，ERK1 / 2和STAT3的磷酸化水平随锌水平而变化，这表明锌可能通过ERK-STAT信号传导影响iPSC的神经分化。总之，我们的研究显示了锌在iPSC神经分化中的重要作用，并提出了iPSC衍生的NSC在神经再生中应用的新思路。