The oncogene Etv5 promotes MET in somatic reprogramming and orchestrates epiblast/primitive endoderm specification during mESCs differentiation.
The oncogene Etv5 promotes MET in somatic reprogramming and orchestrates epiblast/primitive endoderm specification during mESCs differentiation.
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癌基因 Etv5 在体细胞重编程中促进 MET，并在 mESC 分化过程中协调外胚层/原始内胚层规范
DOI：
10.1038/s41419-018-0335-1
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发表时间：
2018-02-14
影响因子：
9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhang J;Cao H;Xie J;Fan C;Xie Y;He X;Liao M;Zhang S;Wang H
单能精原干细胞（SSCs）可以通过调控培养条件而有效地重编程为多能干细胞，而无需引入外源性重编程因子。这种表型提出了这样的假设，即SSCs中的内源性转录因子（TF）可能有助于重编程以获得多能性。在这项研究中，我们筛选了一组SSCs TF（Bcl 6 b，Lhx 1，Foxo 1，Plzf，Id 4，Taf 4 b和Etv 5），发现癌基因Etv 5与Yamanaka因子结合时可以显着提高诱导多能干细胞（iPSCs）生成的效率。我们还证明Etv 5可以通过调节Tet 2-miR 200 s-Zeb 1轴在重编程的早期阶段促进间充质-上皮转化（MET）。此外，Etv 5在小鼠胚胎干细胞（mESC）中的敲低可以通过下调Tet 2来降低基因组5 hmC水平。此外，拟胚体测定显示Etv 5可以通过调节Gata 6正向调节原始内胚层特化，并通过抑制Fgf 5表达来负向调节上胚层特化。总之，我们的研究结果为理解Etv 5在体细胞重编程，mESCs维持和分化背景下的调控机制提供了见解。
Unipotent spermatogonial stem cells (SSCs) can be efficiently reprogrammed into pluripotent stem cells only by manipulating the culture condition, without introducing exogenous reprogramming factors. This phenotype raises the hypothesis that the endogenous transcription factors (TFs) in SSCs may facilitate reprogramming to acquire pluripotency. In this study, we screened a pool of SSCs TFs (Bcl6b, Lhx1, Foxo1, Plzf, Id4, Taf4b, and Etv5), and found that oncogene Etv5 could dramatically increase the efficiency of induced pluripotent stem cells (iPSCs) generation when combined with Yamanaka factors. We also demonstrated that Etv5 could promote mesenchymal-epithelial transition (MET) at the early stage of reprogramming by regulating Tet2-miR200s-Zeb1 axis. In addition, Etv5 knockdown in mouse embryonic stem cells (mESCs) could decrease the genomic 5hmC level by downregulating Tet2. Furthermore, the embryoid body assay revealed that Etv5 could positively regulate primitive endoderm specification through regulating Gata6 and negatively regulate epiblast specification by inhibiting Fgf5 expression. In summary, our findings provide insights into understanding the regulation mechanisms of Etv5 under the context of somatic reprogramming, mESCs maintenance, and differentiation.
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影响因子：
64.8
作者：
Lujan E;Zunder ER;Ng YH;Goronzy IN;Nolan GP;Wernig M
通讯作者：
Wernig M
DOI：
10.1038/nrg3473
发表时间：
2013-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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影响因子：
11.8
作者：
Kang M;Garg V;Hadjantonakis AK
通讯作者：
Hadjantonakis AK
影响因子：
23.9
作者：
Ko, Kinarm;Tapia, Natalia;Schoeler, Hans R.
通讯作者：
Schoeler, Hans R.
影响因子：
11.8
作者：
Chazaud, Claire;Yamanaka, Yojiro;Rossant, Janet
通讯作者：
Rossant, Janet