Critical Role of Tet3 in Neural Progenitor Cell Maintenance and Terminal Differentiation
Critical Role of Tet3 in Neural Progenitor Cell Maintenance and Terminal Differentiation
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Tet3 在神经祖细胞维持和终末分化中的关键作用
DOI：
10.1007/s12035-014-8734-5
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发表时间：
2015-02-01
影响因子：
5.1
通讯作者：
Le, Weidong
中科院分区：
文献类型：
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作者：
Li, Ting;Yang, Dehua;Le, Weidong
5-羟甲基胞嘧啶（5hmC）是由5-甲基胞嘧啶（5mC）由Tet家族双加氧酶（Tet1， Tet2和Tet3）转化而来，在胚胎干细胞（ESCs）和大脑中富集。然而，5hmC和Tet家族在ESC分化特别是神经元分化过程中的作用尚不清楚。在这里，我们展示了Tet3在神经祖细胞（NPC）维持和神经元终末分化中至关重要的证据。我们发现Tet3的表达在ESCs中基本检测不到，但其水平在神经元分化过程中迅速增加。Tet3敲除的ESCs在自我更新和维持方面表现正常，但在神经元分化方面受损。Tet3敲除后的ESCs可以有效地诱导NPC，因为NPC标志物Pax6和nestin的表达与野生型ESCs的NPC相当，但细胞凋亡迅速，神经元的终末分化大大降低。我们的研究结果表明，Tet3在NPC维持和神经元终末分化中起重要作用。
5-Hydroxymethylcytosine (5hmC), converted from 5-methylcytocine (5mC) by Tet family of dioxygenases (Tet1, Tet2, and Tet3), is enriched in the embryonic stem cells (ESCs) and in the brain. However, the role of 5hmC and Tet family in the process of ESC differentiation especially neuronal differentiation remains elusive. Here, we showed the evidence that Tet3 is critical in neural progenitor cell (NPC) maintenance and terminal differentiation of neurons. We found that Tet3 expression is basically undetectable in ESCs, but its level increases rapidly during neuronal differentiation. Tet3 knockout ESCs appear normal in self-renewal and maintenance but impaired in neuronal differentiation. NPCs could be induced efficiently from Tet3 knockout ESCs, as the expression of NPC marker Pax6 and nestin is comparable with NPCs from wild-type ESCs, but undergo apoptosis rapidly, and the terminal differentiation of neurons is greatly reduced. Our results indicate that Tet3 is important for NPC maintenance and terminal differentiation of neurons.