Survivin Improves Reprogramming Efficiency of Human Neural Progenitors by Single Molecule OCT4.

Survivin Improves Reprogramming Efficiency of Human Neural Progenitors by Single Molecule OCT4.
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Survivin 通过单分子 OCT4 提高人类神经祖细胞的重编程效率

DOI:
10.1155/2016/4729535
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发表时间:
2016
影响因子:
4.3
通讯作者:
Li Y
Li Y
中科院分区:
医学3区
文献类型:
--
作者:
Zhou S;Liu Y;Feng R;Wang C;Jiang S;Zhang X;Lan F;Li Y

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通过四种山中因子的异位表达,已在人体细胞中产生了诱导多能干细胞(iPS)。在这里,我们报道了一种凋亡抑制剂Survivin可以与一个因子OCT4 (1F-OCT4-Survivin)一起促进人类神经祖细胞(npc)的iPS细胞生成。与1F-OCT4相比,Survivin加速了人类npc的重编程过程。由1F-OCT4-Survivin生成的神经细胞源性诱导多能干细胞(NiPS)在形态、表面标记、整体基因表达谱和表观遗传状态上与人类胚胎干细胞(hES)细胞相似。Survivin在iPS和ES细胞中均保持高表达。在NiPS细胞向神经细胞分化的过程中,Survivin的表达在蛋白水平上迅速下降。Survivin促进npc重编程效率的机制可能与WNT信号通路中β-catenin的稳定有关。这一假设得到了RT-PCR、染色质免疫沉淀和人类胚胎干细胞Western blot实验的支持。我们的研究结果表明,Survivin的过表达可以通过稳定关键分子β-catenin,通过一个因子OCT4提高npc到iPS细胞的重编程效率。
Induced pluripotent stem (iPS) cells have been generated from human somatic cells by ectopic expression of four Yamanaka factors. Here, we report that Survivin, an apoptosis inhibitor, can enhance iPS cells generation from human neural progenitor cells (NPCs) together with one factor OCT4 (1F-OCT4-Survivin). Compared with 1F-OCT4, Survivin accelerates the process of reprogramming from human NPCs. The neurocyte-originated induced pluripotent stem (NiPS) cells generated from 1F-OCT4-Survivin resemble human embryonic stem (hES) cells in morphology, surface markers, global gene expression profiling, and epigenetic status. Survivin keeps high expression in both iPS and ES cells. During the process of NiPS cell to neural cell differentiation, the expression of Survivin is rapidly decreased in protein level. The mechanism of Survivin promotion of reprogramming efficiency from NPCs may be associated with stabilization of β-catenin in WNT signaling pathway. This hypothesis is supported by experiments of RT-PCR, chromatin immune-precipitation, and Western blot in human ES cells. Our results showed overexpression of Survivin could improve the efficiency of reprogramming from NPCs to iPS cells by one factor OCT4 through stabilization of the key molecule, β-catenin.
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