Repression of SIRT1 Promotes the Differentiation of Mouse Induced Pluripotent Stem Cells into Neural Stem Cells
Repression of SIRT1 Promotes the Differentiation of Mouse Induced Pluripotent Stem Cells into Neural Stem Cells
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SIRT1 的抑制促进小鼠诱导多能干细胞分化为神经干细胞
DOI：
10.1007/s10571-014-0071-8
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发表时间：
2014-08-01
影响因子：
4
通讯作者：
Deng, Zhifeng
中科院分区：
文献类型：
--
作者：
Hu, Bin;Guo, Ye;Deng, Zhifeng
移植来源于诱导多能干细胞（iPSC）的功能性神经干细胞（NSC）用于治疗脑部疾病的使用已经增加。因此，重要的是要了解促进iPSC的NSC分化的分子机制，以用于未来的基于NSC的治疗。Sirtuin 1（SIRT 1）是一种NAD+依赖性蛋白脱乙酰酶，由于其在器官发育、长寿和癌症等过程中的重要作用，在过去十年中引起了人们的极大关注。然而，目前尚不清楚SIRT 1是否在小鼠iPSC向NSC分化中发挥作用。在这项研究中，我们使用补充有视黄酸的无血清培养基从小鼠iPSC产生NSC。然后，我们评估了SIRT 1和调节SIRT 1表达的microRNA-34 a表达的变化。此外，我们使用SIRT 1抑制剂来研究SIRT 1在iPSCs的NSC分化中的作用。数据显示，在此过程中，SIRT 1的表达下降，而miRNAs-34 a的表达增加。此外，SIRT 1的抑制增强了NSC和成熟神经细胞的生成。这表明SIRT 1负调控小鼠iPSC向NSC的分化，并且该过程可能受miRNA-34 a调控。
The use of transplanting functional neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) has increased for the treatment of brain diseases. As such, it is important to understand the molecular mechanisms that promote NSCs differentiation of iPSCs for future NSC-based therapies. Sirtuin 1 (SIRT1), a NAD+-dependent protein deacetylase, has attracted significant attention over the past decade due to its prominent role in processes including organ development, longevity, and cancer. However, it remains unclear whether SIRT1 plays a role in the differentiation of mouse iPSCs toward NSCs. In this study, we produced NSCs from mouse iPSCs using serum-free medium supplemented with retinoic acid. We then assessed changes in the expression of SIRT1 and microRNA-34a, which regulates SIRT1 expression. Moreover, we used a SIRT1 inhibitor to investigate the role of SIRT1 in NSCs differentiation of iPSCs. Data revealed that the expression of SIRT1 decreased, whereas miRNAs-34a increased, during this process. In addition, the inhibition of SIRT1 enhanced the generation of NSCs and mature neurocytes. This suggests that SIRT1 negatively regulated the differentiation of mouse iPSCs into NSCs, and that this process may be regulated by miRNA-34a.