Primary cilia on neural stem/progenitor cells (NSPCs) play an important role in determining cell fate, although the regulatory mechanisms involved in the ciliogenesis remain largely unknown. In this study, we analyzed the effect of the leukemia inhibitory factor (LIF) for the primary cilia in immortalized human NSPCs. LIF withdrawal elongated the primary cilia length, whereas the addition of LIF shortened it. Microarray gene expression analysis revealed that differentially expressed genes (DEGs) associated with LIF treatment were related with the multiple cytokine signaling pathways. Among the DEGs, C-C motif chemokine 2 (CCL2) had the highest ranking and its increase in the protein concentration in the NSPCs-conditioned medium after the LIF treatment was confirmed by ELISA. Interestingly, we found that CCL2 was a negative regulator of cilium length, and LIF-induced shortening of primary cilia was antagonized by CCL2-specific antibody, suggesting that LIF could influence cilia length via upregulating CCL2. The shortening effect of LIF and CCL2 on primary cilia was also observed in SH-SY5Y cells. The results of the study suggested that the LIF-CCL2 axis may well be a regulator of NSPCs and its primary cilia length, which could affect multiple cellular processes, including NSPC proliferation and differentiation.

中文翻译：

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白血病抑制因子通过上调人神经干/祖细胞中的 CC 基序趋化因子 2 缩短初级纤毛

神经干/祖细胞（NSPC）上的初级纤毛在决定细胞命运方面发挥着重要作用，尽管纤毛发生中涉及的调节机制仍然很大程度上未知。在这项研究中，我们分析了白血病抑制因子（LIF）对永生化人类 NSPC 中初级纤毛的影响。LIF 的退出延长了初级纤毛的长度，而添加 LIF 则缩短了初级纤毛的长度。微阵列基因表达分析显示，与 LIF 治疗相关的差异表达基因 (DEG) 与多种细胞因子信号通路相关。在 DEG 中，CC 基序趋化因子 2 (CCL2) 排名最高，并且通过 ELISA 证实了 LIF 处理后 NSPC 条件培养基中蛋白质浓度的增加。有趣的是，我们发现CCL2是纤毛长度的负调节因子，并且LIF诱导的初级纤毛缩短被CCL2特异性抗体拮抗，表明LIF可以通过上调CCL2影响纤毛长度。在 SH-SY5Y 细胞中也观察到 LIF 和 CCL2 对初级纤毛的缩短作用。研究结果表明，LIF-CCL2 轴很可能是 NSPC 及其初级纤毛长度的调节因子，这可能影响多个细胞过程，包括 NSPC 增殖和分化。