Oocyte-Specific Homeobox 1, Obox1, Facilitates Reprogramming by Promoting Mesenchymal-to-Epithelial Transition and Mitigating Cell Hyperproliferation.

Oocyte-Specific Homeobox 1, Obox1, Facilitates Reprogramming by Promoting Mesenchymal-to-Epithelial Transition and Mitigating Cell Hyperproliferation.
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卵母细胞特异性同源盒 1 (Obox1) 通过促进间充质到上皮的转变和减轻细胞过度增殖来促进重编程

DOI:
10.1016/j.stemcr.2017.09.012
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发表时间:
2017-11-14
期刊:
影响因子:
5.9
通讯作者:
Gao S
Gao S
中科院分区:
医学1区
文献类型:
--
作者:
Wu L;Wu Y;Peng B;Hou Z;Dong Y;Chen K;Guo M;Li H;Chen X;Kou X;Zhao Y;Bi Y;Wang Y;Wang H;Le R;Kang L;Gao S

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哺乳动物卵母细胞具有令人着迷的未知因素,可以将终末分化的生殖细胞或体细胞重新编程为全能胚胎。在这里,我们证明了卵母细胞特异性同源盒1(Obox1)是一种卵母细胞特异性因子,可以显著促进小鼠成纤维细胞以非增殖方式诱导多能干细胞(IPSCs)的产生,并可以取代Sox2实现多能性。在OSKM诱导的重编程早期,过表达Obox1可显著促进间充质-上皮转化(MET),同时显著抑制THY1阳性细胞的过度增殖。随后,THY1阴性细胞和Oct4-GFP阳性细胞的比例显著增加。进一步分析Obox1在重编程过程中的基因表达和靶点,表明Obox1的表达可以促进上皮细胞基因的表达,并调节细胞周期相关基因的表达。综上所述,我们得出结论,卵母细胞特异性因子Obox1通过促进MET和缓解细胞过度增殖而成为体细胞重编程的强大激活剂。卵母细胞因子Obox1提高体细胞重编程的效率Obox1可以替代Sox2完成体细胞重编程,Obox1促进MET在体细胞重编程的早期阶段缓解体细胞重编程过程中细胞的过度增殖哺乳动物卵母细胞具有未知因素,可以将分化的细胞重编程为全能胚胎,从而产生新的有机体。在这篇文章中,Gao和他的同事发现Obox1是一种卵母细胞因子,可以通过促进间充质向上皮细胞的转化和减缓细胞的过度增殖来促进体细胞向ipSCs的重编程。
Mammalian oocytes possess fascinating unknown factors, which can reprogram terminally differentiated germ cells or somatic cells into totipotent embryos. Here, we demonstrate that oocyte-specific homeobox 1 (Obox1), an oocyte-specific factor, can markedly enhance the generation of induced pluripotent stem cells (iPSCs) from mouse fibroblasts in a proliferation-independent manner and can replace Sox2 to achieve pluripotency. Overexpression of Obox1 can greatly promote mesenchymal-to-epithelial transition (MET) at early stage of OSKM-induced reprogramming, and meanwhile, the hyperproliferation of THY1-positive cells can be significantly mitigated. Subsequently, the proportion of THY1-negative cells and Oct4-GFP-positive cells increased dramatically. Further analysis of gene expression and targets of Obox1 during reprogramming indicates that the expression of Obox1 can promote epithelial gene expression and modulate cell-cycle-related gene expression. Taken together, we conclude that the oocyte-specific factor Obox1 serves as a strong activator for somatic cell reprogramming through promoting the MET and mitigating cell hyperproliferation. Oocyte factor Obox1 enhances the efficiency of somatic cell reprogramming Obox1 can replace Sox2 to complete somatic cell reprogramming Obox1 promotes MET in the early stage of reprogramming Obox1 mitigates cell hyper-proliferation during somatic cell reprogramming Mammalian oocytes possess unknown factors, which can reprogram differentiated cells into totipotent embryos and thereafter give rise to a new organism. In this article, Gao and colleagues found that Obox1, an oocyte factor, can enhance somatic cell reprogramming to iPSCs by promoting mesenchymal-to-epithelial transition and mitigating cell hyperproliferation.
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